Prevalence And Clinical Significance Of Type Ⅲ Receptor Tyrosine Kinases In Acute Leukemia

Acute myeloid leukemia (AML) is an aggressive malignancy that generally leads to a poor outcome. Deregulated tyrosine kinase activity (RTK) has long been implicated in the molecular pathogenesis of cancer, including leukemia, and mutant forms of FLT3, c-KIT, ABL, and platelet-derived growth factor receptor (PDGFR) among the constitutively activated tyrosine kinases have been identified as causative factors in specific hematologic malignancies.1. Prevalence and clinical significance of FLT3 activating mutations in acute leukemiaFMS-like tyrosine kinase-3 (FLT3), a new member of RTK III subfamily, was originally identified by its expression in hematopoietic stem/progenitor cells, and its importance in normal lymphohematopoietic stem cell function is now well established. Not surprisingly, this receptor appears to play an important role in the pathogenesis of acute leukemia, particularly AML.Two types of FLT3 activating mutation have been reported in leukemia patients: internal tandem duplication(ITD) and point mutation. Both mutations can result in constitutive FLT3 activation. There have been several reports, mainly from Euramerican countries, describing activating mutation of the FLT3 gene. The purpose of this study is to evaluate the prevalence of the two FLT3 activating mutations in Chinese AML patients and its significance.Genomic DNA was screened by polymerase chain reaction (PCR) and gel electrophoresis for FLT3/ITD and point mutation. The FLT3/ITD amplification yielded a higher molecular weight product on a 3% agarose gel stained with ethidium bromide. The point mutation amplification was digested with EcoRV. The digested products were separated on a 3% agarose gel, and undigested PCR product indicated...