Acute Myelogenous Leukemia

We here show that current prognostic tools are not able to adequately assess leukemic evolution and survival outcomes in DDX41-mutant MN. Additional risk factors inherent to this MN subentity hold a prognostic significance beyond the consideration of traditional disease-specific variables, substantiating the need for a dedicated risk scoring system.

It highlights an unusual and serious pattern of relapse in an extramedullary site following blinatumomab therapy. Clinicians should remain vigilant for signs of lineage switch and extramedullary disease during treatment, particularly in patients with KMT2A-rearranged B-ALL, and consider imaging or biopsy when new neurologic or systemic symptoms arise.

These findings unveil therapeutic strategies to potentially prevent leukemic evolution in MPN patients by inhibiting specific cytokine signaling. Our data establish a new paradigm for clonal evolution of blood neoplasms by showing that disease progression in MPN can arise from parallel acute myeloid leukemia (pAML) clones independent of the primary disease.

Among the older cohort, FLT3 and NPM1 mutation status, favorable karyotype, and CCI were not identified as prognostic factors. In the full cohort, using Cox proportional hazard regression and LASSO analyses for age, FLT3 and NPM1 mutation status, cytogenetic risk group, treatment site, race, primary payor, and Charleston Comorbidity Index (CCI), age (HR 65y vs 35y/=2.44, 95% CI 1.61-3.68, p<0.001) was the strongest risk factor in AML.

Although the JAK1/2 inhibitor Ruxolitinib is clinically approved, its efficacy is limited by toxicity to normal cells and the development of drug resistance...Moreover, through a compound screen, followed by chemical proteomics and compound optimization, WWQ-03-012 is discovered, which selectively degrades mutant JAK2, induces primary leukemia cells death, and inhibits MPN progression through targeting DESI2 enzymatic activity in vitro and in vivo. These studies provide a novel therapeutic strategy against mutated JAK2 signaling in MPN and sAML.

P1, N=36, Recruiting, medac GmbH | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Aug 2025 --> Mar 2026

P2, N=25, Not yet recruiting, First Affiliated Hospital of Zhejiang University

P2, N=60, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

DDX6 KO leads to rapid PB dissolution and release of PB-enriched mRNAs, such as BCAT1, into the cytosol, where these transcripts undergo degradation. By reducing BCAT1 levels, DDX6 KO reprograms amino acid metabolism and sensitizes AML cells to cytarabine chemotherapy.

P3, N=1186, Recruiting, Children's Oncology Group | Trial completion date: Sep 2027 --> Jun 2029 | Trial primary completion date: Sep 2027 --> Jun 2029

P1, N=16, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2025 --> Jun 2026

Increased miR-100 levels in CBF-AML (with the t(8;21) subtype included) were associated with poor overall survival (OS); notably, within CBF-AML, the t(8;21) subtype AML patients showed the same trend, where higher miR-99a and miR-100 expression correlated with adverse OS. These findings suggest that regulated expression of miR-99a and miR-100 is common in AML and that their expression correlates with prognosis in CBF-AML.