Human FLT3/FLK2 gene: cDNA cloning and expression in hematopoietic cells

Abstract

The human FLT3 cDNA was cloned from a pre-B cell line and characterized. The deduced amino acid sequence shows that FLT3 codes for a receptor-type tyrosine kinase of 993 residues, presenting a strong similarity with the corresponding mouse FLT3/FLK2 protein as well as with the receptors for colony-stimulating factor 1 (CSF1R/FMS) and steel locus factor (SLFR/KIT). An analysis of the expression of the gene using amplification of reverse transcribed FLT3 mRNA by polymerase chain reaction shows that FLT3 is expressed in various lymphohematopoietic cells and tissues, including a series of immature cell lines and leukemias of lymphocytic origin.

Tandem duplication of the FLT3 gene is found in acute lymphoblastic leukaemia as well as acute myeloid leukaemia but not in myelodysplastic syndrome or juvenile chronic myelogenous leukaemia in children

“…In addition, expression of FLT3 was also reported in many different haemopoietic cell lines including, in particular, pro/pre-B cell lines (Birg et al, 1992;Da Silva et al, 1994;Meierhoff et al, 1995). In haematological malignancies, recent clinical studies showed that FLT3 mRNA was expressed in the majority of patients with B-lineage acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML), especially those containing a monocytic component (Birg et al, 1992;Rosnet et al, 1993;Brasel et al, 1995;Meierhoff et al, 1995;Drexler, 1996).…”

“…Fms-like tyrosine kinase 3 (FLT3), also referred to as fetal liver kinase 2 (flk2) or stem cell tyrosine kinase 1 (STK-1) (Lyman et al, 1993b;Rosnet et al, 1993;Small et al, 1994), located on chromosome 13q12 (Rosnet et al, 1991b), is a class III receptor tyrosine kinase (RTK), along with KIT, FMS and platelet-derived growth-factor receptor (PDGFR) (Matthews et al, 1991;Rosnet et al, 1991a, b;Agnes et al, 1994;Meierhoff et al, 1995), which play a central role in haemopoiesis together with corresponding ligands (Brasel et al, 1995;Carow et al, 1996;Drexler, 1996). RTKs are composed of five immunoglobulin-like subdomains in the extracellular region, a single transmembrane (TM) domain, a juxtamembrane (JM) domain, two intracellular tyrosine kinase domains (TK1 and TK2) divided by a kinase insert (KI) domain, and a C-terminal domain.…”

“…Recently, the ligand for the FLT3 gene has been identified (Lyman et al, 1993a;Hannum et al, 1994). The interaction of FLT3 and its ligand (FL) regulates growth of pluripotent haemopoietic stem cells, early progenitor cells and immature lymphocytes (Rosnet et al, 1993;Brasel et al, 1995;Drexler, 1996), as well as ᭧ 1999 Blackwell Science Ltd Correspondence: Dr Yasuhide Hayashi, Department of Paediatrics, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. leukaemic cells (Piacibello et al, 1995;Carow et al, 1996;Dehmal et al, 1996;Drexler, 1996;Mckenna et al, 1996;Stacchini et al, 1996).…”

“…Initial studies showed that FLT3 was preferentially expressed in haemopoietic stem cells in addition to liver, gonads, placenta, brain and nervous system (Matthews et al, 1991;Rosnet et al, 1991aRosnet et al, , 1993Rossner et al, 1994;Rusten et al, 1996), and was also variably expressed in haematological malignancies (Birg et al, 1992). In respect to haemopoietic cells, FLT3 was expressed predominantly in primitive haemopoietic cells including CD34 þ cells and pro/ pre-B cells.…”

“…In respect to haemopoietic cells, FLT3 was expressed predominantly in primitive haemopoietic cells including CD34 þ cells and pro/ pre-B cells. Thus, it might regulate the early events of haemopoietic development (Rosnet et al, 1993;Small et al, 1994). In addition, expression of FLT3 was also reported in many different haemopoietic cell lines including, in particular, pro/pre-B cell lines (Birg et al, 1992;Da Silva et al, 1994;Meierhoff et al, 1995).…”