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Id2 expression increases with differentiation of human myeloid cells
A Ishiguro, KS Spirin, M Shiohara, A Tobler, AF Gombart, MA Israel, JD Norton and HP Koeffler
Department of Medicine, Cedars-Sinai Medical Center, UCLA School of
Medicine, Los Angeles, CA 90048, USA.
Id proteins are helix-loop-helix (HLH) transcriptional factors that lack
the basic DNA binding domain. The Id proteins have been reported generally
to function as inhibitors of cell differentiation, and their gene
expression is often downregulated during cell differentiation. We examined
the expression of human Id mRNAs by Northern hybridization in 11 human
myeloid cell lines, several myeloid cell lines induced to differentiate,
fresh myeloid leukemia samples, and normal human myeloid cells. Id2 mRNA
was expressed in myelomonoblastic and monoblastic leukemic cells (PLB-985,
THP-1, and U-937) but was weakly expressed in myeloblastic leukemic cells
(KG-1 and HL-60). Id2 mRNA levels markedly increased with induction of
differentiation of myeloid blasts (HL-60, PLB-985, THP-1, and U-937) toward
either granulocytes or macrophages. Examination of fresh acute myeloid
leukemic samples from 22 individuals also showed prominent Id2 mRNA
expression in those samples having more differentiated blasts. Using the
French-American-British classification, only 2 of 8 M0/M1 samples expressed
Id2 mRNA; however, 10 of 13 M2/M3/M4 samples expressed it. In normal human
myeloid cells, Id2 mRNA was expressed in cultured macrophages from bone
marrow and in mature granulocytes and monocytes from peripheral blood. The
half-life of Id2 mRNA was short (1 hour), and its expression was inducible
by cessation of protein synthesis. Id3 mRNA was moderately expressed in
monoblastic cell lines (THP-1 and U-937), and levels decreased with their
differentiation. Almost no Id3 expression was detectable in either other
myeloid leukemia lines, fresh leukemic samples, or normal human myeloid
cells by Northern analyses. Id1 mRNA was not detected by polymerase chain
reaction in either leukemic or normal myeloid cells except in K562
myeloid/erythroid cells. These results showed that Id2 mRNA was
constitutively expressed in more mature myeloid blast cells and level
markedly increased with terminal myeloid differentiation, suggesting that
Id2 protein may inhibit an HLH transcriptional complex that normally
represses myeloid differentiation.
Volume 87,
Issue 12,
pp. 5225-5231,
06/15/1996
Copyright © 1996 by The American Society of Hematology
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