comet-assay-to-quantify-dna-damage-flt3-mutant-expressing-32d-cells

Comet Assay to Quantify DNA Damage in FLT3 Mutant-expressing 32D Cells after Exposure to Type I and Type II FLT3 Inhibitors

FMS-like tyrosine kinase 3 (FLT3), a class III receptor tyrosine kinase, exhibits a mutation frequency of approximately 30% in acute myeloid leukemia ...

canertinib-as-an-flt3-inhibitor-with-potent-activity-against-flt3

Canertinib as an FLT3 Inhibitor with Potent Activity Against FLT3-Mutated and AC220-Resistant Acute Myeloid Leukemia

FMS-like tyrosine kinase 3 (FLT3) mutations are among the most common genetic lesions in acute myeloid leukemia (AML) and are frequently associated with ...

The First Affiliated Hospital of Soochow University

RUNX1 is one of the recurrent mutated genes in newly diagnosed acute myeloid leukemia (AML). Although historically recognized as a provisional distinct entity, the AML subtype with RUNX1 mutations (AML-RUNX1) was eliminated from the 2022 WHO classification system. To gain more insight into the characteristics of AML-RUNX1, we retrospectively analyzed 1065 newly diagnosed adult AML patients from the First Affiliated Hospital of Soochow University between January 2017 and December 2021. RUNX1 mutations were identified in 112 patients (10.5%). The presence of RUNX1 mutation (RUNX1) conferred a lower composite complete remission (CRc) rate (40.2% vs. 58.4%, P＜0.001), but no significant difference was observed in the 5-year overall survival (OS) rate (50.2% vs. 53.9%; HR=1.293; P=0.115) and event-free survival (EFS) rate (51.5% vs. 49.4%; HR=1.487, P=0.089), even within the same risk stratification. Multivariate analysis showed that RUNX1 was not an independent prognostic factor for OS (HR=1.352, P=0.068) or EFS (HR=1.129, P=0.513). When patients were stratified according to induction regimen, RUNX1 was an unfavorable factor for CRc both on univariate and multivariate analysis in patients receiving conventional chemotherapy, and higher risk stratification predicted worse OS. In those who received venetoclax plus hypomethylating agents, RUNX1 was not predictive of CRc and comparable OS and EFS were seen between intermediate-risk and adverse-risk groups. The results of this study revealed that the impact of RUNX1 is limited. Its prognostic value depended more on treatment and co-occurrent abnormalities. VEN-HMA may abrogate the prognostic impact of RUNX1, which merits a larger prospective cohort to illustrate.

Investigations of the prognostic value of RUNX1 mutation in acute myeloid leukemia patients: Data from a real-world study.

T cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is an aggressive malignancy of progenitor T cells. Despite significant improvements in survival of T-ALL/LBL over the past decades, treatment of relapsed and refractory T-ALL (R/R T-ALL/LBL) remains extremely challenging. The prognosis of R/R T-ALL/LBL patients who are intolerant to intensive chemotherapy remains poor. Therefore, innovative approaches are needed to further improve the survival of R/R T-ALL/LBL patients. With the widespread use of next-generation sequencing in T-ALL/LBL, a range of new therapeutic targets such as NOTCH1 inhibitors, JAK-STAT inhibitors, and tyrosine kinase inhibitors have been identified. These findings led to pre-clinical studies and clinical trials of molecular targeted therapy in T-ALL/LBL. Furthermore, immunotherapies such as CD7 CAR T cell therapy and CD5 CAR T cell therapy have shown profound response rate in R/R T-ALL/LBL. Here, we review the progress of targeted therapies and immunotherapies for T-ALL/LBL, and look at the future directions and challenges for the further use of these therapies in T-ALL/LBL.

Targeted therapy and immunotherapy for T cell acute lymphoblastic leukemia/lymphoma.

Venetoclax plus hypomethylating agents in newly diagnosed acute myeloid leukemia patients with RUNX1::RUNX1T1: a retrospective propensity score matching study.

Efficacy and safety of cladribine, low-dose cytarabine and venetoclax in relapsed/refractory acute myeloid leukemia: results of a pilot study.

Clonal evolution from B-cell acute lymphoblastic leukemia with <I>BCR::ABL1</I> multilineage involvement to acute myeloid leukemia after multiple anti-CD19 chimeric antigen receptor T-cell therapy.

The MEF2D rearrangement is a recurrent chromosomal abnormality detected in approximately 2.4-5.3% of patients with acute B-cell lymphoblastic leukemia (B-ALL). Currently, MEF2D-rearranged B-ALL is not classified as an independent subtype in the WHO classification. Consequently, the clinical significance of MEF2D rearrangement in B-ALL remains largely unexplored. In this study, we retrospectively screened 260 B-ALL patients with RNA sequencing data collected between November 2018 and December 2022. Among these, 10 patients were identified with MEF2D rearrangements (4 with MEF2D::HNRNPUL1, 3 with MEF2D::BCL9, 1 with MEF2D::ARID1B, 1 with MEF2D::DAZAP1 and 1 with MEF2D::HNRNPM). Notably, HNRNPM and ARID1B are reported as MEF2D fusion partners for the first time. The patient with the MEF2D::HNRNPM fusion was resistant to chemotherapy and chimeric antigen receptor T-cell therapy and relapsed early after allogenic stem cell transplantation. The patient with MEF2D::ARID1B experienced early extramedullary relapse after diagnosis. All 10 patients achieved complete remission after induction chemotherapy. However, 9/10 (90%) of whom experienced relapse. Three of the 9 patients relapsed with aberrant expression of myeloid antigens. The median overall survival of these patients was only 11 months. This small cohort showed a high incidence of early relapse and short survival in patients with MEF2D rearrangements.

Genetic and clinical characteristics of acute B-cell lymphoblastic leukemia with MEF2D fusions and report of two novel MEF2D rearrangements.

Venetoclax with hypomethylating agents versus intensive chemotherapy in newly diagnosed acute myeloid leukemia with myelodysplasia related changes: A propensity score-matched analysis based on International Consensus Classification.

Quantification of the FLT3 internal tandem duplication is a reliable marker for monitoring measurable residual disease in acute myeloid leukemia with FLT3-ITD mutations.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is theoretically the only curative option for high-risk myelodysplastic syndrome (HR MDS) patients. However, the management of patients with relapsed disease post allo-HSCT remains a challenge with few standard treatments. Chidamide, a new selective histone deacetylase, has shown synergistic anti-leukemia effect combined with azacitidine in acute myeloid leukemia patients. Herein, we reported a 50-year-old HR MDS patient who experienced molecular relapse post allo-HSCT and was successfully salvaged by preemptive treatment of chidamide combined with azacitidine (CHI-AZA). This patient maintained a deep remission lasting over 2 years by regular maintenance treatment of CHI-AZA, without sever treatment-related adverse events or increased risk of graft versus host disease. This case report demonstrated that double epigenetic regimen of CHI-AZA was effective and tolerable. Formally evaluating this regimen in HR MDS patients post allo-HSCT may be meaningful.

Chidamide combined with azacitidine as a novel double epigenetic preemptive treatment for a myelodysplastic syndrome patient showing molecular relapse after allogeneic hematopoietic stem cell transplantation.

Acute myeloid leukemia with myelodysplasia-related changes (AML-MR), a high-risk subtype affecting older patients intolerant to intensive chemotherapy. Venetoclax-based regimens are approved for such patients, while studies suggest priming regimens combining aclarubicin, homoharringtonine or idarubicin and low-dose cytarabine with granulocyte colony-stimulating factor may replace intensive therapy, while direct comparisons are lacking in two groups. This retrospective study compared venetoclax plus hypomethylating agents (VEN+HMA) and priming regimens in 150 propensity score-matched AML-MR patients. VEN+HMA demonstrated superior overall remission (ORR: 78.7% vs. 60.0%,  = 0.013) and complete remission (CR: 48.0% vs. 21.3%,  < 0.001) rates. Notably, VEN+HMA significantly improved median overall survival (OS: not reached vs. 36.37 months,  = 0.026) and event-free survival (EFS: not reached vs. 7.37 months,  = 0.003). Multivariate analysis confirmed VEN+HMA as an independent predictor of better ORR (OR = 2.855,  = 0.014), OS (HR = 0.449,  = 0.036), and EFS (HR = 0.458,  = 0.003). These findings suggest VEN+HMA may be a preferable low-intensity induction therapy over priming regimens for AML-MR.

Venetoclax plus hypomethylating agents versus priming regimen as the first-line therapy for newly diagnosed acute myeloid leukemia with myelodysplasia-related changes: a propensity score-matched analysis.

ArticleTotal : 2	Year
Publication title	2025
Publication title	2025

Article	Year
Investigations of the prognostic value of RUNX1 mutation in acute myeloid leukemia patients: Data from a real-world study. Leukemia research\| PubMed ID: 38493755	2024
Targeted therapy and immunotherapy for T cell acute lymphoblastic leukemia/lymphoma. Annals of hematology\| PubMed ID: 37227492	2023
Venetoclax plus hypomethylating agents in newly diagnosed acute myeloid leukemia patients with RUNX1::RUNX1T1: a retrospective propensity score matching study. Blood cancer journal\| PubMed ID: 38012154	2023
Efficacy and safety of cladribine, low-dose cytarabine and venetoclax in relapsed/refractory acute myeloid leukemia: results of a pilot study. Blood cancer journal\| PubMed ID: 38238305	2024
Clonal evolution from B-cell acute lymphoblastic leukemia with <I>BCR::ABL1</I> multilineage involvement to acute myeloid leukemia after multiple anti-CD19 chimeric antigen receptor T-cell t... Haematologica\| PubMed ID: 38961741	2024
Genetic and clinical characteristics of acute B-cell lymphoblastic leukemia with MEF2D fusions and report of two novel MEF2D rearrangements. Annals of hematology\| PubMed ID: 38990294	2024
Venetoclax with hypomethylating agents versus intensive chemotherapy in newly diagnosed acute myeloid leukemia with myelodysplasia related changes: A propensity score-matched analysis based ... Blood cancer journal\| PubMed ID: 39179571	2024
Quantification of the FLT3 internal tandem duplication is a reliable marker for monitoring measurable residual disease in acute myeloid leukemia with FLT3-ITD mutations. Bone marrow transplantation\| PubMed ID: 39658655	2025
Chidamide combined with azacitidine as a novel double epigenetic preemptive treatment for a myelodysplastic syndrome patient showing molecular relapse after allogeneic hematopoietic stem cel... Annals of hematology\| PubMed ID: 39668198	2024
Venetoclax plus hypomethylating agents versus priming regimen as the first-line therapy for newly diagnosed acute myeloid leukemia with myelodysplasia-related changes: a propensity score-mat... Leukemia & lymphoma\| PubMed ID: 41048093	2025

Yuanhong Huang

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