IDENTIFICATION OF A NOVEL RECEPTOR TYROSINE KINASE EXPRESSED IN ACUTEMYELOID LEUKEMIC BLASTS

Using the polymerase chain reaction with degenerate oligonucleotides d erived from conserved motifs within the catalytic kinase domain of pro tein tyrosine kinases, and RNA extracted from embryonic stem cells, se quences that encode a segment of the kinase domain of several potentia lly novel receptor tyrosine kinases (RTKs) have been identified. One o f these was selected for further study because in Northern analysis it hybridized to RNA from multipotential hematopoietic cell lines, but n ot from lines representative of lineage-committed cells. A cDNA for th is receptor, designated developmental tyrosine kinase (DTK), was isola ted and encodes a protein with structural similarities to AXL. Togethe r these receptors form a new class of RTK. DTK is expressed in a numbe r of human leukemic cell lines, and in the blasts of 6 of 11 patients with acute myeloid leukemia (AML) analyzed, The structure of DTK sugge sts that it may function as a cell adhesion molecule, and mediate cell -to-cell or cell-matrix interactions between hematopoietic cells and t heir respective microenvironments.