NPM1 (Nucleophosmin 1)

P1, N=19, Recruiting, BlueSphere Bio, Inc

This study demonstrated that the variation levels of mutations could provide more accurate prognostic stratification beyond mutation status, offering valuable evidence to refine ELN 2022 risk stratification criteria. Additionally, our established model, combining mutation status or variation levels of genes and cytogenetics, showed excellent prognostic stratification utility, indicating that integration of VAF may effectively improve risk stratification.

P1, N=24, Recruiting, St. Jude Children's Research Hospital | Trial primary completion date: Jul 2026 --> Oct 2026

The modeling results demonstrated a wide therapeutic margin for ziftomenib in adult R/R NPM1-m AML patients and supported a dose of 600 mg once daily in this patient population. Additionally, ER analyses demonstrated that antifungal azoles had no clinically meaningful impact on efficacy or safety profiles and thus could be co-administered with ziftomenib.

P1/2, N=420, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: Jun 2026 --> Feb 2027

P3, N=468, Recruiting, Syndax Pharmaceuticals

XPO1 hyperactivation rewires nucleocytoplasmic transport and sustains leukaemogenic programs in genetically defined acute myeloid leukaemia (AML) subsets. Selective XPO1 inhibitors (selinexor, eltanexor) show preferential activity in NPM1-mutated, DEK::NUP214-positive and SF3B1-mutated myeloid neoplasms. Combination strategies with hypomethylating agents, BCL-2 inhibitors and other targeted therapies enhance depth and durability of responses but are limited by toxicity. Future clinical trials should focus on molecularly selected populations, biomarker-guided dosing and translational endpoints such as measurable residual disease (MRD) and clonal dynamics.

The implementation of a refined LSC detection assay, leveraging CD45RA gating and a stringent LLOQ, yields a specific and clinically actionable quantification of the LSC reservoir in AML. The strong correlation between the CD34 + CD38-CD45RA + LSC subset and MRD status suggests its potential as a complementary biomarker for residual disease monitoring; however, prospective validation in outcome-annotated cohorts is required to establish its prognostic utility and clinical applicability.

This model performed well both in the development cohort (area under the curve [AUC] = 0.817) and multicenter validation cohort (AUC = 0.722). CD135 expression on AML blasts is a pivotal marker that integrates molecular pathogenesis with clinical outcomes, highlighting its dual role as a prognostic indicator and therapeutic target in precision clinical approaches for AM.

P2, N=144, Not yet recruiting, Center for International Blood and Marrow Transplant Research

P=N/A, N=20, Recruiting, The First Affiliated Hospital of Soochow University

P2, N=29, Recruiting, Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias | Active, not recruiting --> Recruiting