Phenotypes and mechanisms in the transformation of hematopoietic cells

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Abstract
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.