Expression of isoforms of the human receptor tyrosine kinase c-kit in leukemic cell lines and acute myeloid leukemia

Blood. 1993 Aug 15;82(4):1151-8.

Abstract

Because mutations in receptor tyrosine kinases may contribute to cellular transformation, studies were undertaken to examine c-kit in human leukemia. Isoforms of c-kit have been characterized in the human megakaryoblastic leukemia cell line M-07. Deletion of the four amino acids Gly-Asn-Asn-Lys in the extracellular domain represents an alternatively spliced isoform that has been shown by others, in mice, to be associated with constitutive receptor autophosphorylation (Reith et al, EMBO J 10:2451, 1991). Additional isoforms differ in the inclusion or exclusion of a serine residue in the interkinase domain, a region that contains the binding site for phosphatidylinositol 3-kinase. By RNase protection analysis, we have shown coexpression of the Gly-Asn-Asn-Lys+ and Gly-Asn-Asn-Lys- isoforms, with dominance of the Gly-Asn-Asn-Lys- transcript, in normal human bone marrow, normal melanocytes, a range of tumor cell lines, and the blasts of 23 patients with acute myeloid leukemia. Analysis of transcripts for the Ser+ and Ser- isoforms also showed coexpression in all normal and leukemic cells examined. The ratios of isoform expression for both the Gly-Asn-Asn-Lys and Ser variants were relatively constant, providing no evidence in the tumors examined that upregulation of one isoform contributes to the neoplastic process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • DNA / analysis
  • Humans
  • Isoenzymes / analysis*
  • Isoenzymes / physiology
  • Leukemia / genetics
  • Leukemia / metabolism*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism*
  • Molecular Sequence Data
  • Phosphorylation
  • Protein-Tyrosine Kinases / analysis*
  • Proto-Oncogene Proteins / analysis*
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-kit
  • Receptors, Cell Surface / analysis*
  • Tumor Cells, Cultured

Substances

  • Isoenzymes
  • Proto-Oncogene Proteins
  • Receptors, Cell Surface
  • DNA
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-kit