FLT3 And C-KIT Receptor Tyrosine Kinase Mutations In Myelodysplastic Syndromes

Background:Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells, characterized by ineffective hematopoiesis of bone marrow and abnormal proliferation.Dysplastic changes in one or more hematopoietic cell lineages, accentuation Bone marrow hyperplasia it also has paramorphia.including pathosis of erythroarray,pathosis of chondrioarray or pathosis thrombopoiesis.MDS is a patho-procedure involving multigene and multisegment. Abnormality of stem cell gene,alteration of hemopoietic microenvironment and defect of immunologic mechanism play importment parts in morbidity. Nowadays,following the extensive and penetrating research of MDS, we find in the disease process of MDS, more and more gene dysfunction have effectiveness to the pathopoiesis. FLT3,c-KIT are the important members of the family receptor tyrosine kinase, the ligands are both stem cell factor. In common circumstance they express in nomal haematopoietic stem/ progenitor cell,early medullary system hematopoietic cell and endothelial cell, to accompany the hematopoietic cell differentiate to the terminal stage,they gradually decrease or even disappear. In the recent days, the research discovers FLT3,c-KIT receptors overexpress or dysexpress in many malignant hematologic diseases。protein tyrosine kinase (PTK)inhibitors, inhibit repair of impaired cancer cells and block cancer cells division. PTKs have become prominent targets for the research and development of new type anticancer drugs that of high performance, low toxicity and strong specificity.Objective:The study is to investigate receptor tyrosine kinase FLT3 and c-KIT recepter expression and FLT3 length mutation (FLT3-LM) in patients with myelodysplastic syndromes (MDS) and their clinical implication. Methods:Mono-nucleus cell are extracted from bone marrow of 38 cases with MDS (23 of high-risk,10 of low-risk) and 10 with non-malignant blood diseases. PCR was used to examine FLT3 gene expression and FLT3-LM. RT-PCR was used to examine c-KIT gene expression.Results:We find 11 FLT3 gene expression of 38 patients with MDS, the expression rate is 28.9%, FLT3-LM were detected in 2 of 11 MDS patients(18.2%), No FLT3-LM was found in 10 controls(P<0.05). We also find 7 c-kit receptor expression in 38 patients with MDS. No c-KIT gene expression was found in 10 controls, the expression rate is 18.4%(P<0.05). Most of FLT3-LM,c-KIT expression patients belong to high-risk patients.Conclusion:FLT3-LM and c-kit expression represent a genetic abnormality in MDS patients. Higher FLT3-LM and c-KIT expression are found in high-risk MDS patients. FLT3-LM and c-KIT expression could be helpful to the pathogenetic condition and prognosis prediction of MDS.