The National Comprehensive Cancer Network (NCCN) defines the following types of acute myeloid leukemia (AML) as favorable-risk: acute promyelocytic leukemia with t(15;17) (APL); AML with core-binding factor (CBF) rearrangements, including t(8;21) and inv(16) or t(16;16) without mutations in KIT (CBF-KIT<sup>wt</sup>); and AML with normal cytogenetics and mutations in NPM1 (NPM1<sup>mut</sup>); or biallelic mutations in CEBPA (CEBPA<sup>mut/mut</sup>), without FLT3-ITD.
Midostaurin is a tyrosine multikinase inhibitor approved for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) with mutated Fms-like tyrosine kinase-3.
According to a two hit model of leukaemogenesis, the association between acute myeloid leukaemia (AML)1 mutations and FLT3 gene alterations has been recently described in M0 AML.
We here report the first clinical case of molecular remission induced by Sorafenib in a patient with FLT3-ITD(+) AML and extramedullary disease after allogenic stem cell transplantation.
In 2017, the US Food and Drug Administration approved four new treatments with indications for fms like tyrosine kinase 3 (FLT3)-mutated AML (midostaurin), newly diagnosed or relapsed/refractory CD33+AML (gemtuzumab ozogamicin), newly diagnosed therapy-related AML or AML with myelodysplasia-related changes (CPX-351) and relapsed/refractory AML with an isocitrate dehydrogenase (IDH)2 mutation (enasidenib).
Activating Flt3 mutations occur in about 30% of patients with acute myeloid leukemia (AML), often as in-frame internal tandem duplication (ITD) at the juxtamembrane domain of the receptor.
FLT3-TKD mutations represented 12.7% of patients, whereas FLT3-internal tandem duplication (ITD) mutation was observed in 20.6% of AML cases and 1.6% of patients harbored both anomalies.
The National Comprehensive Cancer Network (NCCN) defines the following types of acute myeloid leukemia (AML) as favorable-risk: acute promyelocytic leukemia with t(15;17) (APL); AML with core-binding factor (CBF) rearrangements, including t(8;21) and inv(16) or t(16;16) without mutations in KIT (CBF-KIT<sup>wt</sup>); and AML with normal cytogenetics and mutations in NPM1 (NPM1<sup>mut</sup>); or biallelic mutations in CEBPA (CEBPA<sup>mut/mut</sup>), without FLT3-ITD.
Prevalence of FLT3-ITD is as high as 70% among patients with t(6;9) AML, and patients with t(6;9) AML and FLT3-ITD mutations usually have higher white blood cell counts, higher bone marrow blasts, and significantly lower rates of complete remission. t(6;9) is most commonly associated with AML-FAB-M2 and is considered by some researchers to be a separate disease entity because of its distinct clinical and morphologic features and poor prognostic implication.
This review provides a comprehensive analysis of the known discrete and cooperative signaling pathways deregulated by each of the FLT3 specific mutations, as well as the therapeutic approaches that hold the most promise of more durable and personalized therapeutic approaches to improve treatments of FLT3 mutant AML.
Deciphering the mutation spectrum of CEBPAdmAML could facilitate an in-depth understanding of the pathogenesis and refine the prognostic classification of this disease entity.
Targeting of USP10 showed efficacy in preclinical models of mutant-FLT3AML, including cell lines, primary patient specimens and mouse models of oncogenic-FLT3-driven leukemia.
Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm.
The juxtamembrane mutation of FLT3 is the strongest independent marker for disease relapse and is associated with elevated Bcl-2 protein and p53 hyper-phosphorylation in AML.
We have evaluated 9 new molecular markers (ERG, EVI1, MLL-PTD, MN1, PRAME, RHAMM, and WT1 gene-expression levels plus FLT3 and NPM1 mutations) in 121 de novo cytogenetically normal acute myeloblastic leukemias.
Tandem duplication of the FLT3 gene is found in acute lymphoblastic leukaemia as well as acute myeloid leukaemia but not in myelodysplastic syndrome or juvenile chronic myelogenous leukaemia in children.