High expression but no internal tandem duplication of FLT3 in normal hematopoietic cells

The FLT3 gene encodes a tyrosine kinase receptor that regulates proliferati on and differentiation of hematopoietic cells. Recently, the internal dupli cation of FLT3 has been observed in hematological malignancies, suggesting the involvement of these mutations In leukemogenesis. The authors analyzed the expression of FLT3 mRNA and the incidence of its internal tandem duplic ation in normal hematopoietic and blood samples by reverse transcription-po lymerase chain reaction (T-PCR). Mononuclear cells (MNCs) in cord blood and bone marrow highly expressed FLT3 mRNA, whereas MCNs and polymorphonuclear cells (PMNs) in peripheral blood showed low or undetectable levels of FLT3 . When the ratio of FLT3/beta-actin PCR products was calculated the level o f FLT3 mRNA expression was significantly higher in cord blood MNCs (n = 42) than that in peripheral MNCs (n = 14) or PMNs (n =10). Although several PC R bands with different sizes were observed no internal tandem duplication o f FLT3 was defected in these normal blood samples. These findings indicate that the expression of FLT3 is lineage specific and consistently decreases during hematopoietic differentiation. The internal duplication of FLT3 is r estricted in hematological malignancies and may occur at a specific stage i n leukemogenesis.