FLT3 (Fms-related tyrosine kinase 3)

Collectively, our findings define CEBP and ZEB2 alterations as drivers of genetically and clinically distinct subtypes of adult B-ALL and provide a rationale for subtype-specific risk stratification. Preclinical experiments in CEBPalt B-ALL patient-derived xenografts demonstrated sensitivity to FLT3 inhibition, highlighting a potential therapeutic vulnerability.

This aberration is more commonly associated with B-ALL or mixed-phenotype acute leukemia (MPAL-B/M), which are both characterized by lineage plasticity and a higher risk of relapse. These results highlight the importance of comprehensive molecular testing and the need for therapeutic strategies that integrate both myeloid- and lymphoid-directed approaches, as well as meticulous MRD surveillance.

As an exploratory analysis, subtype-specific therapeutic vulnerabilities were revealed: Subtype A displays predicted sensitivity to immune checkpoint inhibitors (anti-PD-1) and tipifarnib, whereas Subtype B responds better to cytarabine/doxorubicin. Crucially, experimental validation confirmed significant upregulation of key model genes (HIP1, SQLE, VNN1) in AML patient samples and cell lines (P < 0.05), reinforcing the model's biological relevance. These findings establish PCD dysregulation as a central axis of AML heterogeneity, providing a framework for precision risk stratification and hypothesis-generating immunophenotype-guided therapy.

P1, N=32, Recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Jun 2026 --> Jun 2028

P1, N=9, Not yet recruiting, Fred Hutchinson Cancer Center

Suspicion for DS should be heightened in patients with acute promyelocytic leukemia (M3 AML) who recently started induction chemotherapy, including all-trans retinoic acid or arsenic trioxide, and in those with non-M3 AML receiving differentiation agents (i.e., isocitrate dehydrogenase inhibitors, menin inhibitors, FMS-like tyrosine kinase 3 inhibitors)... DS represents a diagnostic challenge in the ED due to its nonspecific presentation and mimicry of infection. A high index of suspicion, combined with targeted imaging, laboratory evaluation, and early corticosteroid therapy, can improve outcomes.

Our findings indicate that although OGM excels at resolving complex structural variants, CMA remains essential for detecting copy-neutral events. Until OGM achieves improved sensitivity for CN-LOH, an integrated approach utilizing conventional cytogenetics, CMA, NGS, and OGM provides the most reliable framework for comprehensive genomic assessment across cancer types.

P1, N=38, Recruiting, National Cancer Institute (NCI) | N=28 --> 38

Publicly available single-cell RNA sequencing data further delineated ligand-receptor expression relationships, including Flt3l-Flt3 and Csf2-Csf2ra/Csf2rb axes, within tumor dLNs. These findings reveal remodeling of DC migration, activation, and LNDC turnover within tumor dLNs in the context of CD4+ cell depletion, which enhanced anti-tumor immunity.

After six cycles of azacitidine, she achieved remission of MDS but rapidly progressed to AML and ultimately died. This case provides a key clinical lesson: persistent cytopenias during ibrutinib therapy were attributable to MDS progression rather than SWM, underscoring the importance of re-evaluation. Furthermore, it completely documents clonal evolution from 2.5% blasts (MDS with low blasts) to 6% blasts (MDS with increased blasts-1) and ultimately to AML (66% blasts), and it introduces the emergence of an FLT3-ITD mutation that rapidly drove the disease into AML even after the patient had achieved MDS remission. We also review the rare coexistence of WM and MDS/AML, and MGUS with MDS.

In this large multicenter cohort, KIT and FLT3-ITD mutations did not adversely affect the prognosis of pediatric CBF-AML treated according to the C-HUANAN-AML-15 protocol. MRD after induction was the most powerful predictor of relapse and survival, underscoring its importance for risk stratification in future pediatric AML trials.

P1/2, N=20, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting