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Expression of the Kit and KitA receptor isoforms in human acute myelogenous
leukemia
X Piao, JE Curtis, S Minkin, MD Minden and A Bernstein
Division of Molecular and Developmental Biology, Samuel Lunenfeld Research
Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Genetic and biologic evidence suggests that the Kit receptor tyrosine
kinase is important in early events in hematopoietic stem cell
differentiation. Two naturally occurring isoforms of the Kit receptor,
termed Kit and KitA, were originally described in mouse cells and,
subsequently, in human cells. These isoforms differ by the presence (KitA)
or absence (Kit) of four amino acids (Gly-Asn-Asn-Lys) that lie immediately
outside the transmembrane domain. RNase protection was used to measure the
levels of Kit and KitA mRNA in normal bone marrow and the blast cells from
individuals with acute myelogenous leukemia (AML). Although both isoforms
were present in all the AML samples tested, there was considerable
heterogeneity in the relative levels of the two transcripts, with Kit to
KitA RNA ratios varying from as low as 1.3 to as high as 12. In contrast,
the ratio of Kit to KitA transcripts in normal bone marrow was tightly
clustered between 4.4 and 5.5. Because alterations in the relative levels
of expression of Kit and KitA may affect the ability of a cell to respond
to the Kit ligand, Steel factor, we examined the Kit/KitA RNA ratio in AML
patients that differed with respect to a number of diagnostic, prognostic,
and biologic parameters. The relative levels of Kit to KitA RNA was
independent of French-American-British subtype, response to therapy, and
primary and secondary plating efficiencies in vitro. Thus, these data
suggest that the relative levels of the two isoforms of the Kit receptor in
AML are not associated with any obvious biologic or clinical parameters
and, therefore, may reflect naturally occurring changes in splicing
mechanisms as stem cells differentiate.
Volume 83,
Issue 2,
pp. 476-481,
01/15/1994
Copyright © 1994 by The American Society of Hematology
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