FLT3-ITD and tyrosine kinase domain mutants induce 2 distinct phenotypes in a murine bone marrow transplantation model.

摘要: Activating mutations of the Fms-like tyrosine kinase 3 (FLT3) receptor are most common genetic alteration in acute myeloid leukemia (AML). Two distinct groups FLT3 found: internal tandem duplications (ITDs) juxtamembrane region and point within domain (TKD). Recently, activation loop have also been described childhood lymphoblastic (ALL). FLT3-ITD has shown to induce a myeloproliferative syndrome murine bone marrow transplantation model. The phenotype FLT3-TKD mice not yet investigated. We transduced with retrovirus-expressing mutants or transplanted these cells into lethally irradiated mice. Mice that received transplant developed an oligoclonal disease as previously described. In contrast, induced lymphoid disorder longer latency hematologic manifestations: importantly, induction was due low number cells. manifestation compared together lack influence on clinical outcome patients AML suggest differences cell signaling between FLT3-ITDs. Indeed strong signal transducers activators transcription 5 (STAT5) could only be demonstrated for