The Clinical Prevelence Of FLT3 Mutations In Acute Leukemia

Acute myeloid leukemia (AML) is an aggressive malignancy that generally arises from leukemic stem cells and leads to a poor outcome. Proliferation and differentiation of haematopoietic stem cells are strictly governed by most growth factors and their receptors in which Fms-like tyrosine kinase 3(FLT3) and its ligand (FL) are. Their interaction plays an important role in regulating proliferation differentiation and survival of the haematopoitic stem cells.Recently, most studies have indicated that FLT3 has two classes of activation mutation:internal tandem duplications(ITD) in the juxtamembrane(JM) domain and "activation loop" point mutation in the tyrosine kinase domain and it has approved that they have been the most commom molecular abnormality in the AML patients. Mutant FLT3 exhibit constitutive activity and autophosphorylation in the absence of FL binding,and then causing an aberrant signal transduction pathways,having an oncogenic potential effect by antiapoptosis and differentiation block,furthermore having a important pathological effect on the haematopoietic maliganancy process.On the basis of previous study,we enlarged the samples to further investigate the mutation frequency of FLT3 in the AML patients who are untreated, relapsed, incomplete remission after treatment and complete remission (CR). The relationship between the mutant-wild-type ratio and clinical feature, and the role of the two classes of activating mutations of FLT3 in the process of acute leukemia were assayed. We also investigated whether FLT3 activating mutation could be used as the molecular marker for the detection of minimal residual disease in the leukemia patients.Four hundred and fifty-nine patients were examined for the presence of FLT3 mutations, including: 366 AML patients with -236 de novo AML, 19 relapsed, 30 incmplete remission after treatment and 91 CR; 45 acute lymphoblastic...