MLL rearrangement

Traditional "3+7" chemotherapy regimen with idarubicin plays better in CR induction than that with daunorubicin. But the patient's long-term survival related with clinical practice aspects, like having stem cell transplantation, as well as genetic alterations equally, like MLL rearrangement and DNA methylating related genes' mutations.

P1/2, N=135, The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

All these might exhort differential resistance to treatment. Thus, we found that prognostic and predictive triple biomarkers - KRAS mutated, dual fusions (KMT2A/AFDN, CCDC32/CBX3), and chimeric variants - might evolve with a potential oncogenic role of subclonal evolution for poor clinical outcomes.

Post blinatumomab allogenic stem cell transplantation consolidation was associated with lower risk of CD19- relapse (HR=0.10; 95%CI: 0.03-0.37, p<0.01) and EMD relapse (HR=0.36; 95%CI: 0.18-0.73, p<0.01). In conclusion, leukemia genetics may predict patterns of blinatumomab failure, with TP53m associated with CD19- relapse.

The clinical promise of Revumenib in genetically defined AML highlights its potential role in shaping the future treatment landscape. This mini-review underscores the need for ongoing trials to define optimal dosing, safety protocols, and combination therapies, with the ultimate goal of establishing Revumenib as a standard of care for high-risk AML subsets.

Furthermore, the administration of 30 mg/kg of compound 32d was well tolerated, inhibiting MV-4-11 xenograft growth by 87.1%. Our investigation established the therapeutic effectiveness of the developed WDR5-MLL1/HDAC dual-target inhibitor against acute myeloid leukemia, providing a valuable tool for further exploration of crosstalk between the two targets.

MEN1 inhibitors (MIs), such as revumenib, ziftomenib, and other active small molecules, represent a promising new class of therapies currently under clinical development. It illustrates data from clinical trials and discusses the emergence of resistance mechanisms. In addition, we outline future directions for the use of MIs and emphasize the need for further research to fully realize the potential of these novel compounds, especially in the context of specific genetic subtypes of challenging AL.

Lastly, increased levels of activating methylation in the promoter region of CD44 were identified followed by an upregulation of the oncogenic transcript variant CD44v3 in KMT2A-r T-ALL. Together this suggests that CD44v3 could play a potential role as gene expression-based risk stratification of KMT2A-r rearranged T-ALL and could possibly serve as a therapeutic target using splicing modulators.

Residual KMT2A-r before allo-HSCT independently predicts the risk of survival and relapse, and donor lymphocyte infusion or posttransplantation maintenance therapies should be considered for patients who have AML with detectable molecular MRD.

The study also suggested PI3K inhibitors and Pevonedistat as possible therapeutic options to modulate immune cell infiltration. Our findings confirm the critical role of lactylation in KMT2Ar-AML and identify six key genes that may serve as biomarkers for diagnosis and treatment. In addition to highlighting the need for further validation in clinical settings, these findings contribute to our understanding of KMT2Ar-AML's molecular mechanisms.

Patients were classified into high-risk and low-risk groups based on nomogram scores, with significant differences in OS and CSS between these groups (P < 0.001). This study developed innovative nomograms that combine clinical and treatment factors to predict 1-, 3-, and 5-year survival rates for patients with t (9;11) (p22; q23) AML.

P1, N=24, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Dec 2024 --> Jun 2025