Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Downstream molecular pathways of FLT3 in the pathogenesis of acute myeloid leukemia: biology and therapeutic implications. | Takahashi Journal of Hematology Oncology 2011 4 13 http content 4 1 13 JOURNAL OF HEMATOLOGY ONCOLOGY REVIEW Open Access Downstream molecular pathways of FLT3 in the pathogenesis of acute myeloid leukemia biology and therapeutic implications Shinichiro Takahashi1 2 Abstract FLT3 is a type III receptor tyrosine kinase. Mutations of FLT3 comprise one of the most frequently identified types of genetic alterations in acute myeloid leukemia. One-third of acute myeloid leukemia patients have mutations of this gene and the majority of these mutations involve an internal tandem duplication in the juxtamembrane region of FLT3 leading to constitutive activation of downstream signaling pathways and aberrant cell growth. This review summarizes the current understanding of the effects of the downstream molecular signaling pathways after FLT3 activation with a particular focus on the effects on transcription factors. Moreover this review describes novel FLT3-targeted therapies as well as efficient combination therapies for FLT3-mutated leukemia cells. Introduction FLT3 Fms-like tyrosine kinase 3 is a member of the class III receptor tyrosine kinase family. Notably approximately one-third of acute myeloid leukemia AML patients have mutations of this gene and such mutations are one of the most frequently identified types of genetic alterations in AML. The majority of the mutations involve an internal tandem duplication ITD in the juxtamembrane JM domain of FLT3 which is specifically found in AML 1 . In accordance with the two-hit hypothesis 2 of leukemic transformation FLT3-ITD expression in mouse bone marrow cells expressing a promyelocytic leukemia PML retinoic acid receptor RAR a fusion protein of acute promyelo-cytic leukemia APL caused accelerated malignant transformation 3 . Indeed FLT3-ITD is prevalent 50 in patients with translocations of t 15 17 4 . In addition frequent co-occurrence of mutations of FLT3 with mutations of nucleophosmin NPM 5 and DNA .
