FLT3-ITD mutation

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) showed the highest benefit in the NPM1-mut adverse-risk subgroup. The HARMONY classification provides the basis for a refined genetic risk stratification for adult NPM1-mut AML with potential clinical impact on allo-HSCT decision-making.

Insertion sites located in Hinge Region(HR)/β1 domain and juxtamembrane domain (JMD) derived significantly greater benefit from early FLT3 inhibitor therapy(primarily sorafenib), showing significantly prolonged overall survival...In the era of FLT3-ITD targeted drug therapy combined with transplantation, the insertion site of FLT3-ITD based on high throughput sequencing results helps predict the efficacy of FLT3 inhibitors. Integrating white blood cell count with HR/β1 insertion site can identify a high-risk patient subgroup likely to benefit from FLT3 inhibitor therapy.

P2, N=147, Recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2025 --> May 2029 | Trial primary completion date: Oct 2025 --> May 2029

P1/2, N=73, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> Jan 2028 | Trial primary completion date: Jan 2026 --> Jan 2028

P1/2, N=42, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> Jan 2028 | Trial primary completion date: Jan 2026 --> Jan 2028

This case adds to the limited literature reporting cup-like nuclear morphology in B-ALL, which is typically associated with varied cytogenetic abnormalities, including BCR::ABL1 fusion and hyperdiploidy [3, 4]. The findings emphasize the critical role of FCI and molecular studies in distinguishing AML from B-ALL or mixed phenotype acute leukemias.

Consequently, we constructed an AML xenograft model using cells derived from patients with FLT3-ITD-mutated AML to confirm the efficacy of combining ATGL inhibitors with gilteritinib in vivo. This study provides novel therapeutic targets and monitoring indicators for AML, along with new treatment strategies for patients with FLT3-ITD-mutated AML and those with relapsed/refractory FLT3-ITD-mutated AML.

The FLT3-ITD mutation results in high proliferation and rapid progression of the bone marrow feature in AML patients, with less suppression of normal erythropoiesis. Increased mutation frequency is accompanied by increased leukemic tumor burden in the bone marrow and circulation, and patients with FLT3-ITD mutation have a low response rate to early induction therapy.

Relapsed low-risk AML is often associated with loss of RAS and novel mutations in FLT3-ITD . Age ≥60 years and DNMT3A mutations were identified as independent adverse factors for achieving subsequent remission and post-relapse survival, respectively, while HSCT significantly improved patient outcomes.

Allogeneic hematopoietic stem cell transplantation was associated with better survival, underscoring its significance. These findings reveal the genetic and clinical heterogeneity of NUP98-rearranged AML in adults and support its classification as a distinct entity, highlighting the need for fusion partner-specific therapeutic strategies.

P2, N=19, Active, not recruiting, Centre Antoine Lacassagne | Recruiting --> Active, not recruiting | N=50 --> 19 | Trial completion date: Mar 2027 --> Jul 2028 | Trial primary completion date: Mar 2027 --> Jul 2028

A highly sensitive PCR-NGS assay for FLT3-ITD mutational burden has been developed. Compared with qPCR, PCR-NGS demonstrates superior sensitivity and enables more accurate prediction of posttransplant outcomes in patients with AL undergoing allo-HSCT.