FLT3 (Fms-related tyrosine kinase 3)

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.

Notably, intra-clonal co-localization of NPM1 with IDH1 or TET2 was associated with improved outcomes, whereas co-localization with WT1 predicted dismal prognosis. These results demonstrate that quantitative and structural dimensions of clonality refine the biological and prognostic landscape of NPM1-mutated AML beyond mutational status alone.

P1/2, N=58, Recruiting, Hellenic Society Of Hematology | Not yet recruiting --> Recruiting

Categorizing patients on the basis of MR gene mutations revealed that the inferior survival of sole +8 patients may be attributed to the high frequency of MR gene mutations in these patients. These findings indicate the importance of genetic mutations, specifically MR genes, in sole +8 AML.

These results suggest that concomitant use of quizartinib and moderate CYP3A inducers should be avoided. Concomitant use of weak CYP3A inducers does not warrant dose adjustment, since the impact on quizartinib exposure is clinically nonrelevant.

WT GISTs exhibit considerable molecular heterogeneity with novel or rare mutations of uncertain significance. Targeted NGS enables the detection of clinically relevant alterations that may guide future diagnostic and therapeutic strategies. Our findings emphasize the importance of targeted molecular profiling and raise the potential for personalized treatment in this challenging subset of GISTs.

Here, we define a clinically actionable strategy that functionally targets PLK1 by combining inhibition of the AAA+ ATPase p97/valosin-containing protein (VCP) with the hypomethylating agent decitabine (DAC). In vivo, CB-5339/DAC is well tolerated, significantly prolongs survival, reduces leukemic burden, and suppresses PLK1 in bone marrow blasts. Together, these data establish p97 inhibition as a rational means to exploit replication and proteotoxic stress in AML and provide strong rationale for clinical evaluation of CB-5339 plus DAC in high-risk disease.

P2, N=20, Recruiting, University of Florida | Trial completion date: May 2027 --> May 2028 | Trial primary completion date: May 2026 --> May 2027

P1, N=28, Recruiting, Aspera Biomedicines, Inc. | Not yet recruiting --> Recruiting

Amphotericin B (96.8%) and voriconazole (71.0%) were frequently used, and newer antifungals included isavuconazole (38.7%), olorofim (3.3%), and fosmanogepix (3.3%). Mortality was 22.6% at 1 month, 25.8% at 2 months, 32.3% at 3 months, 41.9% at 6 months, 54.8% at 1 year, 58.1% at 2 years, and 64.5% at 3 years. Despite novel therapies and aggressive surgical interventions, patients with IFS had high mortality.

We describe a 60-year-old man with FLT3-ITD-mutated acute myeloid leukemia (AML) who achieved durable remission following venetoclax-based therapy and a combined HLA-matched sibling HCT-kidney transplant with FLT3 inhibitor maintenance. Four years post-transplant, he developed chronic myelomonocytic leukemia (CMML-1) characterized by re-emergence of driver mutations without FLT3-ITD, marked loss of donor myeloid chimerism, preserved donor T-cell chimerism, and sustained renal allograft function. This case highlights a unique clinical circumstance that may function to recontextualize myelomonocytic features in AML: that they can be attributed to acute leukemias arising from clonal hematopoiesis or occult chronic malignancies, as opposed to de novo AML, particularly given the difficulty in differentiating the two in the acute leukemic setting.

Its mutation subtype, molecular context, treatment setting, assay performance and standardized reporting determine its diagnostic, prognostic, predictive and MRD-related value. This review offers a clinical laboratory perspective on how to interpret FLT3 mutations as actionable biomarkers in AML.