Phenotypes and mechanisms in the transformation of hematopoietic cells.
Interleukin 3 (IL-3) is a growth factor that supports the proliferation of early hematopoietic stem cells, as well as cells that are committed to a variety of the myeloid lineages. The mechanisms by which IL-3 functions have been studied through the use of a series of IL-3-dependent cell lines isolated from myeloid leukemias or long-term bone marrow cultures. A variety of studies have implicated tyrosine phosphorylation in IL-3 signal transduction. One of the substrates of phosphorylation is a 140 kDa, IL-3-binding protein that is speculated to be the biologically relevant IL-3 receptor. IL-3, through tyrosine phosphorylation, supports viability and growth through the regulation of transcription of a series of genes including c-myc and c-pim-1. The c-myc gene contributes to viability, in part, by regulating the transcription of the ornithine decarboxylase gene. The role of growth factors in differentiation is less clear. By studying IL-3-dependent myeloid leukemia cell lines, two genes have been identified whose altered expression is associated with blocking the ability of the cells to differentiate. The c-myb gene is a nuclear DNA binding protein that has been implicated in myeloid transformation in a number of systems. The Evi-1 gene is a novel gene of the zinc finger family of transcriptional activators. Possible mechanisms by which these genes interfere with normal differentiation are discussed.
Ihle
J N
JN
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
Morishita
K
K
Bartholomew
C
C
Matsugi
T
T
Askew
D
D
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics; D008667:Metalloproteins / Q000235:genetics; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000378:metabolism
D004268:DNA-Binding Proteins; D008667:Metalloproteins; D011505:Protein-Tyrosine Kinases