FLT3 Mutations: Biology and Treatment

摘要: FLT3 is a receptor tyrosine kinase with important roles in hematopoietic stem/progenitor cell survival and proliferation. It mutated about 1/3 of acute myeloid leukemia (AML) patients, either by internal tandem duplications (ITD) the juxtamembrane domain or point mutations usually involving (KD). Both types mutation constitutively activate FLT3. Many studies have shown that AML patients FLT3/ITD poor cure rates due to relapse. This has led development number small molecule inhibitors (TKI) activity against these are still preclinical development, but several entered clinical phase I II trials as monotherapy relapsed AML. Patients responses, most often clearing peripheral blasts, rarely major reductions bone marrow blasts. Several was successfully inhibited patients. However, complete remissions been achieved trials. The difference responses chronic (CML) BCR-ABL compared mutant may be reflective treating single gene disease CML versus multiply altered testing TKI combination conventional chemotherapy, trial designs based on showing synergistic effects between agents inducing cytotoxic responses. ongoing planned both newly diagnosed FLT3-mutant