Acute Myelogenous Leukemia

P=N/A, N=27, Recruiting, Institute of Hematology & Blood Diseases Hospital, China | Not yet recruiting --> Recruiting

P2, N=30, Not yet recruiting, Stanford University

Moreover, Compound 14 demonstrated an impressive pharmacokinetic profile and exerted significant antitumor efficacy in the FLT3-ITD-positive AML xenograft mouse model (approximately 80% decrease in tumor mass). Also, biochemical blood analysis and histopathological studies revealed that Compound 14 demonstrated a good safety profile.

P1/2, N=249, Active, not recruiting, Molecular Partners AG | Recruiting --> Active, not recruiting | Trial completion date: Dec 2029 --> May 2027 | Trial primary completion date: Dec 2027 --> May 2026

P1, N=16, Active, not recruiting, Children's Oncology Group | Trial completion date: Mar 2026 --> Dec 2026

P=N/A, N=50, Not yet recruiting, The First Affiliated Hospital of Soochow University

P1, N=82, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting

Given the differing cytogenetics among each cell population, the CLL and AML may have developed as separate clonal processes. With a further understanding of the pathogenic mechanism, this may influence the treatment decision-making process.

Lastly, an exploratory cross-disease comparison showed that MRD-negative (MRDneg) hrMDS patients had similar survival outcomes to MRD-positive (MRDpos) AML patients. These findings demonstrate the prognostic value of MFC-MRD in intensively treated hrMDS and provide rationale for prospective trials of MRD-informed transplant and post-remission strategies.

ACSL4-high blasts showed enhanced dasatinib sensitivity (r = -0.25, P = 4.3 x 10-8). Conversely, ACSL4-high blasts showed significant ex vivo resistance to venetoclax (r = 0.36, P = 2.5 x 10-12), linking the ferroptosis-primed monocytic state to BCL2 inhibitor failure. These findings nominate ACSL4-driven ferroptosis susceptibility as a lineage-specific vulnerability rendering monocytic AML selectively sensitive to SRC-directed therapy while resistant to BCL2 inhibition.

Single-cell analysis identified 17 distinct cell populations and 14 cell types, revealing cell-specific expression patterns of these risk genes across different hematopoietic lineages. This integrative approach provides robust evidence for causal relationships between specific genetic factors and AML risk, offering insights into disease mechanisms and potential therapeutic targets at the cellular level.

Pretransplant treatment was intentionally limited to 2-3 cycles: three cycles of Aza in Case 1, intensive induction chemotherapy followed by one cycle of Aza in Case 2, and two cycles of venetoclax plus Aza in Case 3. In addition, for patients with FISH-detectable TP53 abnormalities, serial FISH may provide a practical adjunct for pretransplant decision-making in routine practice. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.