JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Palliative care development in the Asia-Pacific region: an international survey from the Asia Pacific Hospice Palliative Care Network (APHN).
BMJ Support Palliat Care
PUBLISHED: 07-12-2014
Show Abstract
Hide Abstract
Although palliative care is an important public healthcare issue worldwide, the current situation in the Asia-Pacific region has not been systematically evaluated.
Related JoVE Video
Repressed BMP signaling reactivates NKL homeobox gene MSX1 in a T-ALL subset.
Leuk. Lymphoma
PUBLISHED: 05-22-2014
Show Abstract
Hide Abstract
In T-cell acute lymphoblastic leukemia (T-ALL), several members of the NK-like (NKL) homeobox genes are aberrantly expressed. Here, we have analyzed the activity of NKL homeobox gene MSX1 using pediatric T-ALL in silico data, detecting overexpression in 11% of patients. Quantification of MSX1 transcripts in a panel of 24 T-ALL cell lines demonstrated overexpression in two examples. Comparative expression profiling indicated inhibition of the bone morphogenetic protein (BMP) signaling pathway, which was shown to inhibit MSX1 transcription. In the LOUCY cell line we identified conspicuous expression of CHRDL1 encoding a BMP inhibitor which mediated activation of MSX1. Promoter analyses demonstrated activation of CHRDL1 by oncogenic PITX1. Furthermore, knockdown and overexpression studies of hematopoietic transcription factors demonstrated that GATA2 and FOXC1 mediate activation and GATA3, LEF1, TAL1 and TOX repression of MSX1 transcription. Collectively, our findings suggest that MSX1 is physiologically restricted to lymphoid progenitors. The identification of deregulated BMP signaling may provide novel therapeutic options for the treatment of T-ALL.
Related JoVE Video
Deregulated FOX genes in Hodgkin lymphoma.
Genes Chromosomes Cancer
PUBLISHED: 03-28-2014
Show Abstract
Hide Abstract
FOX genes encode transcription factors which regulate basic developmental processes during embryogenesis and in the adult. Several FOX genes show deregulated expression in particular malignancies, representing oncogenes or tumor suppressors. Here, we screened six Hodgkin lymphoma (HL) cell lines for FOX gene activity by comparative microarray profiling, revealing overexpression of FOXC1 and FOXD1, and reduced transcription of FOXN3, FOXO1, and FOXP1. In silico expression analyses of these FOX gene candidates in HL patient samples supported the cell line data. Chromosomal analyses demonstrated an amplification of the FOXC1 locus at 6p25 and a gain of the FOXR2 locus at Xp11, indicting genomic aberrations for their upregulation. Comparative expression profiling and ensuing stimulation experiments revealed implementation of the TGF?- and WNT-signaling pathways in deregulation of FOXD1 and FOXN3. Functional analysis of FOXP1 implicated miR9 and miR34a as upstream regulators and PAX5, TCF3, and RAG2 as downstream targets. A similar exercise for FOXC1 revealed repression of MSX1 and activation of IPO7, both mediating inhibition of the B-cell specific homeobox gene ZHX2. Taken together, our data show that aberrantly expressed FOX genes and their downstream targets are involved in the pathogenesis of HL via deregulation of B-cell differentiation and may represent useful diagnostic markers and/or therapeutic targets.
Related JoVE Video
A recurrent 11q aberration pattern characterizes a subset of MYC-negative high-grade B-cell lymphomas resembling Burkitt lymphoma.
Blood
PUBLISHED: 01-07-2014
Show Abstract
Hide Abstract
The genetic hallmark of Burkitt lymphoma (BL) is the t(8;14)(q24;q32) and its variants leading to activation of the MYC oncogene. It is a matter of debate whether true BL without MYC translocation exists. Here, we identified 59 lymphomas concordantly called BL by 2 gene expression classifiers among 753 B-cell lymphomas. Only 2 (3%) of these 59 molecular BL lacked a MYC translocation, which both shared a peculiar pattern of chromosome 11q aberration characterized by interstitial gains including 11q23.2-q23.3 and telomeric losses of 11q24.1-qter. We extended our analysis to 17 MYC-negative high-grade B-cell lymphomas with a similar 11q aberration and showed this aberration to be recurrently associated with morphologic and clinical features of BL. The minimal region of gain was defined by high-level amplifications in 11q23.3 and associated with overexpression of genes including PAFAH1B2 on a transcriptional and protein level. The recurrent region of loss contained a focal homozygous deletion in 11q24.2-q24.3 including the ETS1 gene, which was shown to be mutated in 4 of 16 investigated cases. These findings indicate the existence of a molecularly distinct subset of B-cell lymphomas reminiscent of BL, which is characterized by deregulation of genes in 11q.
Related JoVE Video
The voices of young New Zealanders involved in pediatric palliative care.
J Palliat Care
PUBLISHED: 12-31-2013
Show Abstract
Hide Abstract
The perspectives of young New Zealanders receiving pediatric palliative care (PPC) are not well understood. A qualitative study of the perceptions of 16 PPC patients and their siblings, aged 9 to 18, was conducted through audio and written diary accounts. Inductive thematic analysis revealed several concerns. of participants, including special treatment that patients had received, spending time with their families, their feelings of being judged or discriminated against, their sense of being understood themselves and of understanding others, and mortality. A nonjudgemental, open approach is recommended when consulting with patients and their siblings in order to determine their needs.
Related JoVE Video
Siblings Caring for and about Pediatric Palliative Care Patients.
J Palliat Med
PUBLISHED: 12-06-2013
Show Abstract
Hide Abstract
Abstract Background: The experiences of young people who have siblings with life-limiting illnesses are not well understood. Aim: The study proposed to identify the concerns of siblings of pediatric palliative care (PPC) patients. Design and Measurement: Semistructured interviews were administered to participants and analyzed using qualitative inductive thematic analysis. Setting and Participants: Study subjects were 18 siblings of PPC patients aged 9 to 22 living in the Auckland area. Results: The siblings of PPC patients held concerns about their siblings impending death and desires to be involved in their lives and care. Conclusions: Siblings may benefit from opportunities to be involved in conversations about mortality and the care of their ill sibling. They are able to express their concerns and help provide care to PPC patients.
Related JoVE Video
Perceptions of physically active men with prostate cancer on the role of physical activity in maintaining their quality of life: possible influence of androgen deprivation therapy.
Psychooncology
PUBLISHED: 07-02-2013
Show Abstract
Hide Abstract
The primary aim of this study was to examine the perceptions of older men with prostate cancer regarding their quality of life and physical activity post-diagnosis, and the potential benefits and risks associated with being physically active. A secondary aim was to gain some preliminary insight into how these perceptions may differ as a function of androgen deprivation therapy (ADT).
Related JoVE Video
Classical and molecular cytogenetic analysis.
Methods Mol. Biol.
PUBLISHED: 05-03-2013
Show Abstract
Hide Abstract
Cytogenetic analysis is performed on cell cultures for several reasons, notably, to perform identity checks by verifying species of origin or the retention of key chromosome rearrangements in cell lines described previously. De novo chromosome analysis is usually performed when characterizing cancer cell lines for the presence of neoplastic rearrangements associated with specific tumors. This usually involves fluorescence in situ hybridization (FISH) using clones covering gene loci near recurrent chromosome breakpoints. Chromosome breakage is an important endpoint in radiation biology and mutagenesis, enabling cell lines to be used for measuring genotoxic dosage and repair. Finally, cytogenetic analysis may be performed to monitor stability in culture. Unlike most preparative techniques, chromosome preparation resists standardization. Hence, procedures must be optimized for each cell line. Thus, evidence-based protocols are described for hypotonic harvesting, rapid G-banding, FISH, and Spectral Karyotyping (SKY) analysis of cell cultures to allow troubleshooting and fine-tuning to suit the requirements of individual cell lines.
Related JoVE Video
Chromothripsis in Hodgkin lymphoma.
Genes Chromosomes Cancer
PUBLISHED: 03-11-2013
Show Abstract
Hide Abstract
Chromosomal rearrangements are common features of most cancers, where they contribute to deregulated gene expression. Chromothripsis is a recently described oncogenic mechanism whereby small genomic pieces originating from one chromosomal region undergo massive rearrangements in a single step. Here, we document chromothripsis in Hodgkin lymphoma (HL) cell lines by genomic profiling, showing alternating amplicons of defined chromosomal regions. In L-1236 cells, fluorescent in situ hybridization analyses identified aberrations affecting amplified chromosomal segments that derived from the long arm regions of chromosomes 3 and 9 and that colocalized to a derivative chromosome 6, indicating the cataclysmic origin of this mutation. The ABL1 gene at 9q34 was targeted by these rearrangements leading to its overexpression in L-1236 cells, correlating with pharmacological resistance to treatment with the kinase inhibitor dasatinib. Collectively, we identified and characterized chromothriptic rearrangements in HL cell lines to serve as models for analyzing this novel oncogenomic mechanism.
Related JoVE Video
t(8;9)(p22;p24)/PCM1-JAK2 activates SOCS2 and SOCS3 via STAT5.
PLoS ONE
PUBLISHED: 01-23-2013
Show Abstract
Hide Abstract
Fusions of the tyrosine kinase domain of JAK2 with multiple partners occur in leukemia/lymphoma where they reportedly promote JAK2-oligomerization and autonomous signalling, Affected entities are promising candidates for therapy with JAK2 signalling inhibitors. While JAK2-translocations occur in myeloid, B-cell and T-cell lymphoid neoplasms, our findings suggest their incidence among the last group is low. Here we describe the genomic, transcriptional and signalling characteristics of PCM1-JAK2 formed by t(8;9)(p22;p24) in a trio of cell lines established at indolent (MAC-1) and aggressive (MAC-2A/2B) phases of a cutaneous T-cell lymphoma (CTCL). To investigate signalling, PCM1-JAK2 was subjected to lentiviral knockdown which inhibited 7 top upregulated genes in t(8;9) cells, notably SOCS2/3. SOCS3, but not SOCS2, was also upregulated in a chronic eosinophilic leukemia bearing PCM1-JAK2, highlighting its role as a central signalling target of JAK2 translocation neoplasia. Conversely, expression of GATA3, a key T-cell developmental gene silenced in aggressive lymphoma cells, was partially restored by PCM1-JAK2 knockdown. Treatment with a selective JAK2 inhibitor (TG101348) to which MAC-1/2A/2B cells were conspicuously sensitive confirmed knockdown results and highlighted JAK2 as the active moiety. PCM1-JAK2 signalling required pSTAT5, supporting a general paradigm of STAT5 activation by JAK2 alterations in lymphoid malignancies. MAC-1/2A/2B--the first JAK2-translocation leukemia/lymphoma cell lines described--display conspicuous JAK/STAT signalling accompanied by T-cell developmental and autoimmune disease gene expression signatures, confirming their fitness as CTCL disease models. Our data support further investigation of SOCS2/3 as signalling effectors, prognostic indicators and potential therapeutic targets in cancers with JAK2 rearrangements.
Related JoVE Video
Inhibition of PI3K/mTOR Overcomes Nilotinib Resistance in BCR-ABL1 Positive Leukemia Cells through Translational Down-Regulation of MDM2.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Chronic myeloid leukemia (CML) is a cytogenetic disorder resulting from formation of the Philadelphia chromosome (Ph), that is, the t(9;22) chromosomal translocation and the formation of the BCR-ABL1 fusion protein. Tyrosine kinase inhibitors (TKI), such as imatinib and nilotinib, have emerged as leading compounds with which to treat CML. t(9;22) is not restricted to CML, 20-30% of acute lymphoblastic leukemia (ALL) cases also carry the Ph. However, TKIs are not as effective in the treatment of Ph+ ALL as in CML. In this study, the Ph+ cell lines JURL-MK2 and SUP-B15 were used to investigate TKI resistance mechanisms and the sensitization of Ph+ tumor cells to TKI treatment. The annexin V/PI (propidium iodide) assay revealed that nilotinib induced apoptosis in JURL-MK2 cells, but not in SUP-B15 cells. Since there was no mutation in the tyrosine kinase domain of BCR-ABL1 in cell line SUP-B15, the cells were not generally unresponsive to TKI, as evidenced by dephosphorylation of the BCR-ABL1 downstream targets, Crk-like protein (CrkL) and Grb-associated binder-2 (GAB2). Resistance to apoptosis after nilotinib treatment was accompanied by the constitutive and nilotinib unresponsive activation of the phosphoinositide 3-kinase (PI3K) pathway. Treatment of SUP-B15 cells with the dual PI3K/mammalian target of rapamycin (mTOR) inhibitor BEZ235 alone induced apoptosis in a low percentage of cells, while combining nilotinib and BEZ235 led to a synergistic effect. The main role of PI3K/mTOR inhibitor BEZ235 and the reason for apoptosis in the nilotinib-resistant cells was the block of the translational machinery, leading to the rapid downregulation of the anti-apoptotic protein MDM2 (human homolog of the murine double minute-2). These findings highlight MDM2 as a potential therapeutic target to increase TKI-mediated apoptosis and imply that the combination of PI3K/mTOR inhibitor and TKI might form a novel strategy to combat TKI-resistant BCR-ABL1 positive leukemia.
Related JoVE Video
Massive transcriptional perturbation in subgroups of diffuse large B-cell lymphomas.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Based on the assumption that molecular mechanisms involved in cancerogenesis are characterized by groups of coordinately expressed genes, we developed and validated a novel method for analyzing transcriptional data called Correlated Gene Set Analysis (CGSA). Using 50 extracted gene sets we identified three different profiles of tumors in a cohort of 364 Diffuse large B-cell (DLBCL) and related mature aggressive B-cell lymphomas other than Burkitt lymphoma. The first profile had high level of expression of genes related to proliferation whereas the second profile exhibited a stromal and immune response phenotype. These two profiles were characterized by a large scale gene activation affecting genes which were recently shown to be epigenetically regulated, and which were enriched in oxidative phosphorylation, energy metabolism and nucleoside biosynthesis. The third and novel profile showed only low global gene activation similar to that found in normal B cells but not cell lines. Our study indicates novel levels of complexity of DLBCL with low or high large scale gene activation related to metabolism and biosynthesis and, within the group of highly activated DLBCLs, differential behavior leading to either a proliferative or a stromal and immune response phenotype.
Related JoVE Video
Ectopic expression of homeobox gene NKX2-1 in diffuse large B-cell lymphoma is mediated by aberrant chromatin modifications.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Homeobox genes encode transcription factors ubiquitously involved in basic developmental processes, deregulation of which promotes cell transformation in multiple cancers including hematopoietic malignancies. In particular, NKL-family homeobox genes TLX1, TLX3 and NKX2-5 are ectopically activated by chromosomal rearrangements in T-cell neoplasias. Here, using transcriptional microarray profiling and RQ-PCR we identified ectopic expression of NKL-family member NKX2-1, in a diffuse large B-cell lymphoma (DLBCL) cell line SU-DHL-5. Moreover, in silico analysis demonstrated NKX2-1 overexpression in 5% of examined DLBCL patient samples. NKX2-1 is physiologically expressed in lung and thyroid tissues where it regulates differentiation. Chromosomal and genomic analyses excluded rearrangements at the NKX2-1 locus in SU-DHL-5, implying alternative activation. Comparative expression profiling implicated several candidate genes in NKX2-1 regulation, variously encoding transcription factors, chromatin modifiers and signaling components. Accordingly, siRNA-mediated knockdown and overexpression studies confirmed involvement of transcription factor HEY1, histone methyltransferase MLL and ubiquitinated histone H2B in NKX2-1 deregulation. Chromosomal aberrations targeting MLL at 11q23 and the histone gene cluster HIST1 at 6p22 which we observed in SU-DHL-5 may, therefore, represent fundamental mutations mediating an aberrant chromatin structure at NKX2-1. Taken together, we identified ectopic expression of NKX2-1 in DLBCL cells, representing the central player in an oncogenic regulative network compromising B-cell differentiation. Thus, our data extend the paradigm of NKL homeobox gene deregulation in lymphoid malignancies.
Related JoVE Video
A randomised feasibility study of EPA and Cox-2 inhibitor (Celebrex) versus EPA, Cox-2 inhibitor (Celebrex), resistance training followed by ingestion of essential amino acids high in leucine in NSCLC cachectic patients--ACCeRT study.
BMC Cancer
PUBLISHED: 10-17-2011
Show Abstract
Hide Abstract
Cancer cachexia is a syndrome of progressive weight loss. Non-small cell lung cancer patients experience a high incidence of cachexia of 61%. Research into methods to combat cancer cachexia in various tumour sites has recently progressed to the combination of agents.The combination of the anti-cachectic agent Eicosapentaenoic acid (EPA) and the cyclo-oxygenase-2 (COX-2) inhibitor celecoxib has been tested in a small study with some benefit. The use of progressive resistance training (PRT) followed by the oral ingestion of essential amino acids (EAA), have shown to be anabolic on skeletal muscle and acceptable in older adults and other cancer groups.The aim of this feasibility study is to evaluate whether a multi-targeted approach encompassing a resistance training and nutritional supplementation element is acceptable for lung cancer patients experiencing cancer cachexia.
Related JoVE Video
Transcriptional deregulation of homeobox gene ZHX2 in Hodgkin lymphoma.
Leuk. Res.
PUBLISHED: 09-16-2011
Show Abstract
Hide Abstract
Recently, we identified a novel chromosomal rearrangement in Hodgkin lymphoma (HL), t(4;8)(q27;q24), which targets homeobox gene ZHX2 at the recurrent breakpoint 8q24. This aberration deletes the far upstream region of ZHX2 and results in silenced transcription pinpointing loss of activatory elements. Here, we have looked for potential binding sites within this deleted region to analyze the transcriptional deregulation of this tumor suppressor gene in B-cell malignancies. SiRNA-mediated knockdown and reporter gene analyses identified two transcription factors, homeodomain protein MSX1 and bZIP protein XBP1, directly regulating ZHX2 expression. Furthermore, MSX1-cofactor histone H1C mediated repression of ZHX2 and showed enhanced expression levels in cell line L-1236. As demonstrated by fluorescence in situ hybridization and genomic array analysis, the gene loci of MSX1 at 4p16 and H1C at 6p22 were rearranged in several HL cell lines, correlating with their altered expression activity. The expression of XBP1 was reduced in 6/7 HL cell lines as compared to primary hematopoietic cells. Taken together, our results demonstrate multiple mechanisms decreasing expression of tumor suppressor gene ZHX2 in HL cell lines: loss of enhancing binding sites, reduced expression of activators MSX1 and XBP1, and overexpression of MSX1-corepressor H1C. Moreover, chromosomal deregulations of genes involved in this regulative network highlight their role in development and malignancy of B-cells.
Related JoVE Video
Mutations of PHF6 are associated with mutations of NOTCH1, JAK1 and rearrangement of SET-NUP214 in T-cell acute lymphoblastic leukemia.
Haematologica
PUBLISHED: 08-31-2011
Show Abstract
Hide Abstract
Mutations in the PHF6 gene were recently described in patients with T-cell acute lymphoblastic leukemia and in those with acute myeloid leukemia. The present study was designed to determine the prevalence of PHF6 gene alterations in T-cell acute lymphoblastic leukemia.
Related JoVE Video
Neoplastic MiR-17~92 deregulation at a DNA fragility motif (SIDD).
Genes Chromosomes Cancer
PUBLISHED: 08-03-2011
Show Abstract
Hide Abstract
Chromosomal or mutational activation of BCL6 (at 3q27) typifies diffuse large B-cell lymphoma (DLBCL) which in the germinal center subtype may be accompanied by focal amplification of chromosome band 13q31 effecting upregulation of miR-17~92. Using long distance inverse-polymerase chain reaction, we mapped and sequenced six breakpoints of a complex BCL6 rearrangement t(3;13)(q27;q31)t(12;13)(p11;q31) in DLBCL cells, which places miR-17~92 antisense within the resulting ITPR2-BCL6 chimeric fusion gene rearrangement. MiR-17~92 members were upregulated ~15-fold over controls in a copy number independent manner consistent with structural deregulation. MIR17HG and ITPR2-BCL6 were, despite their close configuration, independently expressed, discounting antisense regulation. MIR17HG in t(3;13)t(12;13) cells proved highly responsive to treatment with histone deacetylase inhibitors implicating epigenetic deregulation, consistent with which increased histone-H3 acetylation was detected by chromatin immunoprecipitation near the upstream MIR17HG breakpoint. Remarkably, 5/6 DNA breaks in the t(3;13)t(12;13) precisely cut at stress-induced DNA duplex destabilization (SIDD) peaks reminiscent of chromosomal fragile sites, while the sixth lay 150 bp distant. Extended SIDD profiling showed that additional oncomiRs also map to SIDD peaks. Fluorescence in situ hybridization analysis showed that 11 of 52 (21%) leukemia-lymphoma (L-L) cell lines with 13q31 involvement bore structural rearrangements at/near MIR17HG associated with upregulation. As well as fueling genome instability, SIDD peaks mark regulatory nuclear-scaffold matrix attachment regions open to nucleosomal acetylation. Collectively, our data indict a specific DNA instability motif (SIDD) in chromosome rearrangement, specifically alterations activating miR-17~92 epigenetically via promoter hyperacetylation, and supply a model for the clustering of oncomiRs near cancer breakpoints.
Related JoVE Video
t(4;8)(q27;q24) in Hodgkin lymphoma cells targets phosphodiesterase PDE5A and homeobox gene ZHX2.
Genes Chromosomes Cancer
PUBLISHED: 06-01-2011
Show Abstract
Hide Abstract
Hodgkin/Reed-Sternberg (HRS) cells represent the malignant fraction of infiltrated lymph nodes in Hodgkin lymphoma (HL). Although HRS cells display multiple chromosomal aberrations, few are recurrent and the targeted genes unknown. However, understanding the pathology of HL and developing rational therapies may well require identifying putative deregulated genes. Here, we analyzed the karyotype of the well-defined HL cell line L-1236 by spectral karyotyping and identified multiple abnormalities, therein, notably t(4;8)(q27;q24) which includes two breakpoint regions previously highlighted in HL. Target genes at 4q27 and 8q24 were shortlisted by high density genomic arrays and fluorescence in situ hybridization. Expression analysis of candidate target genes revealed conspicuous activation of phosphodiesterase PDE5A at 4q27 and inhibition of homeobox gene ZHX2 at 8q24. Treatment of L-1236 with PDE5A-inhibitor sildenafil or with siRNA directed against PDE5A and concomitant stimulation with cyclic guanosine monophosphate (cGMP) resulted in enhanced apoptosis, indicating PDE5A as an oncogene. Expression profiling of L-1236 cells following siRNA-mediated knockdown of ZHX2 showed inhibition of genes regulating differentiation and apoptosis, suggesting tumor suppressor activity of ZHX2. Downstream genes included STAT1 and several STAT1-target genes, indicating activation of STAT1-signaling by ZHX2 as analyzed by RQ-PCR and western blot. Taken together, we have identified a novel aberration with recurrent breakpoints in HL, t(4;8)(q27;q24), which activate PDE5A and repress ZHX2, deregulating apoptosis, differentiation, and STAT1-signaling in HL cells.
Related JoVE Video
Molecular breakpoint analysis of chromosome translocations in cancer cell lines by Long Distance Inverse-PCR.
Methods Mol. Biol.
PUBLISHED: 04-26-2011
Show Abstract
Hide Abstract
With conventional cytogenetic screening by fluorescence in situ hybridization (FISH) using genomic tilepath clones, identification of genes in oncogenic chromosome translocations is often laborious, notably if the region of interest is gene-dense. Conventional molecular methods for partner identification may also suffer severe limitations; for instance, genomic PCR screening requires prior knowledge of both sets of breakpoints, while rapid amplification of cDNA ends (RACE) is not only limited to translocations causing mRNA fusion, but also fails to provide potentially relevant breakpoint data. With Long Distance Inverse (LDI)-PCR, however, it is theoretically possible to identify unknown translocation partners and to map the breakpoints down to the base pair level. Implementing LDI-PCR only requires approximate sequence information on one partner, rendering it ideal for use in combination with frontline FISH analysis. The protocol described here has been tuned for use by those wishing to identify new cancer genes in tumor cell lines.
Related JoVE Video
Cytogenetic analysis of cancer cell lines.
Methods Mol. Biol.
PUBLISHED: 04-26-2011
Show Abstract
Hide Abstract
Cancer genes are often deregulated by genomic rearrangements. Accordingly, analysis of the participant chromosomes responsible now occupies a key role in characterizing and identifying cancer cell lines. Cytogenetics may also be used to study the nature and extent of chromosome breakage induced by radiation or chemicals ("clastogenesis"), to distinguish individual cells or clones within a tumor cell population and to monitor the stability of chromosome rearrangements. This chapter describes cytogenetic procedures for characterizing cancer cells in culture. Cell lines allow the use of a wider range of harvesting and hypotonic treatments to optimize metaphase chromosome preparations than that possible with primary cultures. This assists improved banding, fluorescence in situ hybridization (FISH), and Spectral Karyotyping (SKY) analysis for research, rendering cell lines ideal tools for oncogenomics, ideally in parallel with transcriptomic analysis of the same cells. The experience of the writers with more than 800 cell lines has shown that no single hypotonic harvesting protocol is adequate consistently to deliver satisfactory chromosome preparations. Thus, evidence-based protocols are described for hypotonic harvesting, rapid G-banding, and FISH and SKY analysis of cell cultures to allow troubleshooting and fine-tuning to suit the requirements of individual cell lines.
Related JoVE Video
Activation of Paired-homeobox gene PITX1 by del(5)(q31) in T-cell acute lymphoblastic leukemia.
Leuk. Lymphoma
PUBLISHED: 03-22-2011
Show Abstract
Hide Abstract
In T-cell acute lymphoblasic leukemia (T-ALL), neoplastic chromosomal rearrangements are known to deregulate members of the homeobox gene families NKL and HOXA. Here, analysis of T-ALL cell lines and primary cells identified aberrant expression of a third homeobox gene group, the Paired (PRD) class. LOUCY cells revealed chromosomal deletion at 5q31, which targets the downstream regulatory region of the PRD homeobox gene PITX1, removing a STAT1 binding site. STAT1 mediates repressive interleukin 2 (IL2)-STAT1 signaling, implicating IL2 pathway avoidance as a possible activation mechanism. Among primary T-ALL samples, 2/22 (9%) aberrantly expressed PITX1, highlighting the importance of this gene. Forced expression of PITX1 in JURKAT cells and subsequent target gene analysis prompted deregulation of genes involved in T-cell development including HES1, JUN, NKX3-1, RUNX1, RUNX2, and TRIB2. Taken together, our data show leukemic activation of PITX1, a novice PRD-class homeobox gene in a subset of early-staged T-ALL, which may promote leukemogenesis by inhibiting T-cell development.
Related JoVE Video
Body composition, physical fitness, functional performance, quality of life, and fatigue benefits of exercise for prostate cancer patients: a systematic review.
J Pain Symptom Manage
PUBLISHED: 03-02-2011
Show Abstract
Hide Abstract
Prostate cancer patients, especially those on androgen deprivation therapy (ADT), experience many symptoms that make it difficult to maintain their independence and quality of life. Because ADT acts by means of reducing testosterone production, exercise may offset many of the ADT side effects and those of the cancer itself.
Related JoVE Video
Transcriptional deregulation of oncogenic myocyte enhancer factor 2C in T-cell acute lymphoblastic leukemia.
Leuk. Lymphoma
PUBLISHED: 01-24-2011
Show Abstract
Hide Abstract
Myocyte enhancer factor 2C (MEF2C) encodes a transcription factor which is ectopically expressed in T-cell acute lymphoblastic leukemia (T-ALL) cell lines, deregulated directly by ectopically expressed homeodomain protein NKX2-5 or by loss of promoter regions via del(5)(q14). Here, we analyzed the MEF2C 5-region, thus identifying potential regulatory binding sites for GFI1B, basic helix-loop-helix proteins, STAT5, and HOXA9/HOXA10. Chromatin immunoprecipitation and overexpression analyses demonstrated direct activation by GFI1B and LYL1 and inhibition by STAT5. HOXA9/HOXA10 activated expression of NMYC which in turn mediated MEF2C repression, indicating an indirect mode of regulation via NMYC interactor (NMI) and STAT5. Lacking comma: Chromosomal deletion of the STAT5 binding site in LOUCY cells reduced protein levels of STAT5 in some MEF2C-positve T-ALL cell lines, and the presence of inhibitory IL7-JAK-STAT5 signaling highlighted the repressive impact of this factor in MEF2C regulation. Taken together, our results indicate that the expression of MEF2C in T-ALL cells is principally deregulated via activating leukemic transcription factors GFI1B or NKX2-5 and by escaping inhibitory developmental STAT5 signaling.
Related JoVE Video
History of leukemia-lymphoma cell lines.
Hum. Cell
PUBLISHED: 10-04-2010
Show Abstract
Hide Abstract
We outline the near 50-year history of leukemia-lymphoma (LL) cell lines - a key model system in biomedicine. Due to the detailed documentation of their oncogenomic and transcriptional alterations via recent advances in molecular medicine, LL cell lines may be fitted to parent tumors with a degree of precision unattainable in other cancers. We have surveyed the corpus of published LL cell lines and found 637 examples that meet minimum standards of authentication and characterization. Alarmingly, the rate of establishment of new LL cell lines has plummeted over the last decade. Although the main hematopoietic developmental cell types are represented by cell lines, some LL categories stubbornly resist establishment in vitro. The advent of engineering techniques for immortalizing primary human cells that maintain differentiation means the time is ripe for renewed search for in vitro models from un(der)represented hematologic entities. Given their manifold applications in biomedicine, there is little doubt that LL-derived cell lines will continue to play a vital part well into the next half-century as well.
Related JoVE Video
What does care mean? Perceptions of people approaching the end of life.
Palliat Support Care
PUBLISHED: 09-28-2010
Show Abstract
Hide Abstract
This project sought to better understand the nature of medical care from the perspective of people approaching the end of life.
Related JoVE Video
Polycomb repressor complex 2 regulates HOXA9 and HOXA10, activating ID2 in NK/T-cell lines.
Mol. Cancer
PUBLISHED: 06-17-2010
Show Abstract
Hide Abstract
NK- and T-cells are closely related lymphocytes, originating from the same early progenitor cells during hematopoiesis. In these differentiation processes deregulation of developmental genes may contribute to leukemogenesis. Here, we compared expression profiles of NK- and T-cell lines for identification of aberrantly expressed genes in T-cell acute lymphoblastic leukemia (T-ALL) which physiologically regulate the differentiation program of the NK-cell lineage.
Related JoVE Video
Amplification at 11q23 targets protein kinase SIK2 in diffuse large B-cell lymphoma.
Leuk. Lymphoma
PUBLISHED: 04-07-2010
Show Abstract
Hide Abstract
In diffuse large B-cell lymphoma (DLBCL), several recurrent chromosomal aberrations have been described where the presumed target genes remain unknown, including gain/amplification at 11q23-24. Here, we characterized amplification at 11q23 in the DLBCL cell line KARPAS-422. Quantitative genomic PCR and FISH analysis were used to define the region altered, thus showing an amplification peak at 111.1 Mb, the region hosting SIK2/SNF1LK2. Expression profiling, quantitative RT-PCR, Western blot, and immunocytology identified overexpression of SIK2, highlighting this gene as a likely key target of 11q23 amplification. SIK2 encodes a protein kinase that has been shown to inhibit transcription factor CREB via phosphorylation of its cofactor TORC2/CRTC2. Accordingly, siRNA-mediated downregulation of SIK2 expression resulted in upregulation of the CREB target gene BIM. Functional analysis by treatments with cAMP, the glucocorticoid dexamethasone, and 2-deoxy-d-glucose revealed a regulatory role for SIK2 in survival and glucose metabolism, respectively. However, overexpression of SIK2 was not detectable in primary DLBCL samples. Nevertheless, identification of SIK2 as an amplification target highlights this kinase along with its regulatory network as potential therapeutic targets in DLBCL.
Related JoVE Video
Recommendation of short tandem repeat profiling for authenticating human cell lines, stem cells, and tissues.
In Vitro Cell. Dev. Biol. Anim.
PUBLISHED: 03-30-2010
Show Abstract
Hide Abstract
Cell misidentification and cross-contamination have plagued biomedical research for as long as cells have been employed as research tools. Examples of misidentified cell lines continue to surface to this day. Efforts to eradicate the problem by raising awareness of the issue and by asking scientists voluntarily to take appropriate actions have not been successful. Unambiguous cell authentication is an essential step in the scientific process and should be an inherent consideration during peer review of papers submitted for publication or during review of grants submitted for funding. In order to facilitate proper identity testing, accurate, reliable, inexpensive, and standardized methods for authentication of cells and cell lines must be made available. To this end, an international team of scientists is, at this time, preparing a consensus standard on the authentication of human cells using short tandem repeat (STR) profiling. This standard, which will be submitted for review and approval as an American National Standard by the American National Standards Institute, will provide investigators guidance on the use of STR profiling for authenticating human cell lines. Such guidance will include methodological detail on the preparation of the DNA sample, the appropriate numbers and types of loci to be evaluated, and the interpretation and quality control of the results. Associated with the standard itself will be the establishment and maintenance of a public STR profile database under the auspices of the National Center for Biotechnology Information. The consensus standard is anticipated to be adopted by granting agencies and scientific journals as appropriate methodology for authenticating human cell lines, stem cells, and tissues.
Related JoVE Video
Check your cultures! A list of cross-contaminated or misidentified cell lines.
Int. J. Cancer
PUBLISHED: 02-10-2010
Show Abstract
Hide Abstract
Continuous cell lines consist of cultured cells derived from a specific donor and tissue of origin that have acquired the ability to proliferate indefinitely. These cell lines are well-recognized models for the study of health and disease, particularly for cancer. However, there are cautions to be aware of when using continuous cell lines, including the possibility of contamination, in which a foreign cell line or microorganism is introduced without the handlers knowledge. Cross-contamination, in which the contaminant is another cell line, was first recognized in the 1950s but, disturbingly, remains a serious issue today. Many cell lines become cross-contaminated early, so that subsequent experimental work has been performed only on the contaminant, masquerading under a different name. What can be done in response-how can a researcher know if their own cell lines are cross-contaminated? Two practical responses are suggested here. First, it is important to check the literature, looking for previous work on cross-contamination. Some reports may be difficult to find and to make these more accessible, we have compiled a list of known cross-contaminated cell lines. The list currently contains 360 cell lines, drawn from 68 references. Most contaminants arise within the same species, with HeLa still the most frequently encountered (29%, 106/360) among human cell lines, but interspecies contaminants account for a small but substantial minority of cases (9%, 33/360). Second, even if there are no previous publications on cross-contamination for that cell line, it is essential to check the sample itself by performing authentication testing.
Related JoVE Video
What can people approaching death teach us about how to care?
Patient Educ Couns
PUBLISHED: 02-05-2010
Show Abstract
Hide Abstract
This study sought to hear what patients approaching death had to say about doctor-patient interactions and care in order that doctors can learn how to demonstrate care more effectively so that each patient feels cared for as an individual.
Related JoVE Video
NK-like homeodomain proteins activate NOTCH3-signaling in leukemic T-cells.
BMC Cancer
PUBLISHED: 05-12-2009
Show Abstract
Hide Abstract
Homeodomain proteins control fundamental cellular processes in development and in cancer if deregulated. Three members of the NK-like subfamily of homeobox genes (NKLs), TLX1, TLX3 and NKX2-5, are implicated in T-cell acute lymphoblastic leukemia (T-ALL). They are activated by particular chromosomal aberrations. However, their precise function in leukemogenesis is still unclear. Here we screened further NKLs in 24 T-ALL cell lines and identified the common expression of MSX2. The subsequent aim of this study was to analyze the role of MSX2 in T-cell differentiation which may be disturbed by oncogenic NKLs.
Related JoVE Video
Multiple mechanisms induce ectopic expression of LYL1 in subsets of T-ALL cell lines.
Leuk. Res.
PUBLISHED: 04-20-2009
Show Abstract
Hide Abstract
Basic helix-loop-helix (bHLH) transcription factors are essential for lymphocytic differentiation. Here, we have analyzed the complete bHLH family in T-cell acute lymphoblastic leukemia cell lines by expression profiling. Differential expression was detected for BHLHB2, HES1, HES4, HEY1, ID1, ID2, ID3, LYL1 and TAL1, highlighting dysregulation of family members with inhibitory activity. Subsequently we focused on the mechanisms responsible for aberrant expression of LYL1 in comparison to TAL1. Quantitative genomic PCR indicated microdeletions upstream of both, TAL1 and LYL1, targeting STIL/SIL and TRMT1, respectively. Additionally, one LYL1-expressing cell line exhibited amplification of TRMT1. While deletion of STIL correlated with expression of the STIL-TAL1 fusion transcript, no TRMT-LYL1 fusion transcripts were detected in parallel with genomic rearrangements thereof. Sequence analysis of the LYL1 promoter region revealed potential binding sites for transcription factors HOXA10, LMO2 and NKX2-5. Overexpression analysis, reporter gene assays and chromatin immuno-precipitation confirmed their activating impact on LYL1 expression. In conclusion, we identified multiple mechanisms which activate LYL1 in leukemic cells, including structural genomic alterations, namely microdeletion or amplification, together with the involvement of prominent oncogenic transcription factors.
Related JoVE Video
New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic, and transcriptional profiling.
Blood
PUBLISHED: 04-14-2009
Show Abstract
Hide Abstract
Lymphomas are assumed to originate at different stages of lymphocyte development through chromosomal aberrations. Thus, different lymphomas resemble lymphocytes at distinct differentiation stages and show characteristic morphologic, genetic, and transcriptional features. Here, we have performed a microarray-based DNA methylation profiling of 83 mature aggressive B-cell non-Hodgkin lymphomas (maB-NHLs) characterized for their morphologic, genetic, and transcriptional features, including molecular Burkitt lymphomas and diffuse large B-cell lymphomas. Hierarchic clustering indicated that methylation patterns in maB-NHLs were not strictly associated with morphologic, genetic, or transcriptional features. By supervised analyses, we identified 56 genes de novo methylated in all lymphoma subtypes studied and 22 methylated in a lymphoma subtype-specific manner. Remarkably, the group of genes de novo methylated in all lymphoma subtypes was significantly enriched for polycomb targets in embryonic stem cells. De novo methylated genes in all maB-NHLs studied were expressed at low levels in lymphomas and normal hematopoietic tissues but not in nonhematopoietic tissues. These findings, especially the enrichment for polycomb targets in stem cells, indicate that maB-NHLs with different morphologic, genetic, and transcriptional background share a similar stem cell-like epigenetic pattern. This suggests that maB-NHLs originate from cells with stem cell features or that stemness was acquired during lymphomagenesis by epigenetic remodeling.
Related JoVE Video
Many are called MDS cell lines: one is chosen.
Leuk. Res.
PUBLISHED: 02-05-2009
Show Abstract
Hide Abstract
Myelodysplastic syndromes (MDS) comprise a heterogenous group of clonal disorders of hematopoietic progenitors, showing genetic instability and in many cases progression to acute myeloid leukemia (AML). When MDS progress towards AML (AML/MDS), additional genetic lesions cause a block in differentiation and an accumulation of blast cells. Hence, both pathophysiologically and clinically the MDS and AML/MDS phases are distinguishable. Leukemia cell lines are key resources for modelling hematological malignancies. Characterization of these cell lines has provided a rich vein of insights into the mechanisms underlying malignant transformation. Some 31 cell lines have been described in the literature purportedly established from patients with MDS. However, a significant minority of these has proved false after DNA profiling which revealed their cross-contamination with older established leukemia cell lines. Most remaining ("authentic") MDS cell lines were established during the leukemic phase of the disease progression rather than during the MDS phase. Based on these data we have assigned the 31 candidate MDS cell lines to one of the three categories: (1) false (cross-contaminated) cell lines and non-malignant cell lines; (2) malignant cell lines established in the AML/MDS leukemic phase; and (3) apparently legitimate MDS cell lines established during the MDS phase. While MDS and AML/MDS cell lines both provide singular resources for modelling pathology, mining oncogenically modified macromolecules, and testing druggability, we contend these groups should be considered separately.
Related JoVE Video
SET-NUP214 fusion in acute myeloid leukemia- and T-cell acute lymphoblastic leukemia-derived cell lines.
J Hematol Oncol
PUBLISHED: 01-23-2009
Show Abstract
Hide Abstract
SET-NUP214 fusion resulting from a recurrent cryptic deletion, del(9)(q34.11q34.13) has recently been described in T-cell acute lymphoblastic leukemia (T-ALL) and in one case of acute myeloid leukemia (AML). The fusion protein appears to promote elevated expression of HOXA cluster genes in T-ALL and may contribute to the pathogenesis of the disease. We screened a panel of ALL and AML cell lines for SET-NUP214 expression to find model systems that might help to elucidate the cellular function of this fusion gene.
Related JoVE Video
Activation of miR-17-92 by NK-like homeodomain proteins suppresses apoptosis via reduction of E2F1 in T-cell acute lymphoblastic leukemia.
Leuk. Lymphoma
PUBLISHED: 01-17-2009
Show Abstract
Hide Abstract
The NK-like family of homeobox genes includes TLX1, TLX3 and NKX2-5, which are ectopically activated in distinct subsets of T-cell acute lymphoblastic leukemia (T-ALL) cells. Here we analysed their effect on the miR-17-92 cluster overexpressed in several types of cancer, including T-ALL. The pri-miR-17-92 polycistron encodes micro-RNAs (miRNAs), which decrease E2F1 protein expression, regulating proliferation and/or apoptosis. Quantification of pri-miR-17-92 in T-ALL cell lines suggested an implication of the NK-like homeodomain proteins in transcriptional regulation. Lentiviral-mediated overexpression of NKX2-5 in the T-ALL cell line MOLT-4 consistently resulted in increased miR-17-92 pri-miRNA levels and decreased amounts of E2F1 protein. Induction of apoptosis by treating miR17-92 or E2F1 transduced T-ALL cells with etoposide led to reduced or enhanced cell viability, respectively. Furthermore, analysis of pri-miR-17-92 in T-ALL patients indicated elevated expression in those bearing TLX1/3 positive cells. These data support an activatory effect of NK-like homeodomain proteins on pri-miR-17-92 expression and concomitantly reduced E2F1 protein levels, thereby enhancing survival of leukemic T-cells.
Related JoVE Video
Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing.
Nat. Genet.
Show Abstract
Hide Abstract
Burkitt lymphoma is a mature aggressive B-cell lymphoma derived from germinal center B cells. Its cytogenetic hallmark is the Burkitt translocation t(8;14)(q24;q32) and its variants, which juxtapose the MYC oncogene with one of the three immunoglobulin loci. Consequently, MYC is deregulated, resulting in massive perturbation of gene expression. Nevertheless, MYC deregulation alone seems not to be sufficient to drive Burkitt lymphomagenesis. By whole-genome, whole-exome and transcriptome sequencing of four prototypical Burkitt lymphomas with immunoglobulin gene (IG)-MYC translocation, we identified seven recurrently mutated genes. One of these genes, ID3, mapped to a region of focal homozygous loss in Burkitt lymphoma. In an extended cohort, 36 of 53 molecularly defined Burkitt lymphomas (68%) carried potentially damaging mutations of ID3. These were strongly enriched at somatic hypermutation motifs. Only 6 of 47 other B-cell lymphomas with the IG-MYC translocation (13%) carried ID3 mutations. These findings suggest that cooperation between ID3 inactivation and IG-MYC translocation is a hallmark of Burkitt lymphomagenesis.
Related JoVE Video
Match criteria for human cell line authentication: where do we draw the line?
Int. J. Cancer
Show Abstract
Hide Abstract
Continuous human cell lines have been used extensively as models for biomedical research. In working with these cell lines, researchers are often unaware of the risk of cross-contamination and other causes of misidentification. To reduce this risk, there is a pressing need to authenticate cell lines, comparing the sample handled in the laboratory to a previously tested sample. The American Type Culture Collection Standards Development Organization Workgroup ASN-0002 has developed a Standard for human cell line authentication, recommending short tandem repeat (STR) profiling for authentication of human cell lines. However, there are known limitations to the technique when applied to cultured samples, including possible genetic drift with passage. In our study, a dataset of 2,279 STR profiles from four cell banks was used to assess the effectiveness of the match criteria recommended within the Standard. Of these 2,279 STR profiles, 1,157 were grouped into sets of related cell lines-duplicate holdings, legitimately related samples or misidentified cell lines. Eight core STR loci plus amelogenin were used to unequivocally authenticate 98% of these related sets. Two simple match algorithms each clearly discriminated between related and unrelated samples, with separation between related samples at ?80% match and unrelated samples at <50% match. A small degree of overlap was noted at 50-79% match, mostly from cell lines known to display variable STR profiles. These match criteria are recommended as a simple and effective way to interpret results from STR profiling of human cell lines.
Related JoVE Video
Transcriptional activation of prostate specific homeobox gene NKX3-1 in subsets of T-cell lymphoblastic leukemia (T-ALL).
PLoS ONE
Show Abstract
Hide Abstract
Homeobox genes encode transcription factors impacting key developmental processes including embryogenesis, organogenesis, and cell differentiation. Reflecting their tight transcriptional control, homeobox genes are often embedded in large non-coding, cis-regulatory regions, containing tissue specific elements. In T-cell acute lymphoblastic leukemia (T-ALL) homeobox genes are frequently deregulated by chromosomal aberrations, notably translocations adding T-cell specific activatory elements. NKX3-1 is a prostate specific homeobox gene activated in T-ALL patients expressing oncogenic TAL1 or displaying immature T-cell characteristics. After investigating regulation of NKX3-1 in primary cells and cell lines, we report its ectopic expression in T-ALL cells independent of chromosomal rearrangements. Using siRNAs and expression profiling, we exploited NKX3-1 positive T-ALL cell lines as tools to investigate aberrant activatory mechanisms. Our data confirmed NKX3-1 activation by TAL1/GATA3/LMO and identified LYL1 as an alternative activator in immature T-ALL cells devoid of GATA3. Moreover, we showed that NKX3-1 is directly activated by early T-cell homeodomain factor MSX2. These activators were regulated by MLL and/or by IL7-, BMP4- and IGF2-signalling. Finally, we demonstrated homeobox gene SIX6 as a direct leukemic target of NKX3-1 in T-ALL. In conclusion, we identified three major mechanisms of NKX3-1 regulation in T-ALL cell lines which are represented by activators TAL1, LYL1 and MSX2, corresponding to particular T-ALL subtypes described in patients. These results may contribute to the understanding of leukemic transcriptional networks underlying disturbed T-cell differentiation in T-ALL.
Related JoVE Video
Clinical, immunophenotypic, cytogenetic, and molecular genetic features in 117 adult patients with mixed-phenotype acute leukemia defined by WHO-2008 classification.
Haematologica
Show Abstract
Hide Abstract
Among 4,780 consecutive adult acute lymphoblastic/myeloblastic leukemia patients, we identified 117 (2.4%) patients with mixed-phenotype acute leukemia fulfilling WHO 2008 criteria; these were classified as: Blymphoid+ myeloid (n=64), T-lymphoid+myeloid (n=38), B+T-lymphoid (n=14) and trilineage (n=1). Of 92 patients karyotyped, 59 were abnormal and were classified as: complex (22 of 92), t(9;22)(q34;q11) (14 of 92), monosomy 7 (7 of 92), polysomy 21 (7 of 92), t(v;11q23) (4 of 92), t(10;11)(p15;q21) (3 of 92), while STIL-TAL1 fusion was detected in one (T+My) patient. After investigating common acute leukemia-related mutations in 17 genes, 12 of 31 (39%) patients were found to have at least one mutation, classified with: IKZF1 deletion (4 of 31), and EZH2 (3 of 31), ASXL1 (3 of 31), ETV6 (2 of 31), NOTCH1 (1 of 31), and TET2 (1 of 31) mutations. Array-CGH revealed genomic deletions of CDKN2A (4 of 12), IKZF1 (3 of 12), MEF2C (2 of 12), BTG1 (2 of 12), together with BCOR, EBF1, K-RAS, LEF1, MBNL1, PBX3, and RUNX1 (one of 12 each). Our results indicate that mixed-phenotype acute leukemia is a complex entity with heterogeneous clinical, immunophenotypic, cytogenetic, and molecular genetic features.
Related JoVE Video
Oncogenic deregulation of NKL homeobox gene MSX1 in mantle cell lymphoma.
Leuk. Lymphoma
Show Abstract
Hide Abstract
ABSTRACT NKL homeobox gene MSX1 is physiologically expressed during embryonic hematopoiesis. Here, we detected MSX1 overexpression in three examples from mantle cell lymphoma (MCL) and one from acute myeloid leukemia (AML) by screening 96 leukemia/lymphoma cell lines via microarray profiling. Moreover, in silico analysis identified significant overexpression of MSX1 in 3% each of MCL and AML patients confirming aberrant activity in subsets of both types of malignancies. Comparative expression profiling analysis and subsequent functional studies demonstrated overexpression of histone acetyltransferase PHF16 together with transcription factors FOXC1 and HLXB9 as activators of MSX1 transcription. Additionally, we identified regulation of cyclinD1/CCND1 by MSX1 and its repressive cofactor histone H1C. Fluorescence in situ hybridization in MCL cells showed that t(11;14)(q13;q32) results in detachment of CCND1 from its corresponding repressive MSX1 binding site. Together, we uncovered regulators and targets of homeobox gene MSX1 in leukemia/lymphoma cells supporting the view of a recurrent genetic network which is reactivated in malignant transformation.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.