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bcl-2 proto-oncogene expression in normal and neoplastic human myeloid
cells
D Delia, A Aiello, D Soligo, E Fontanella, C Melani, F Pezzella, MA Pierotti and G Della Porta
Istituto Nazionale per Lo Studio e La Cura Dei Tumori, Milan, Italy.
The present study provides immunobiochemical and molecular data on the
differentiation-linked expression of the bcl-2 proto-oncogene in normal and
neoplastic myeloid cells. Using a recently developed monoclonal antibody
(MoAb) to the bcl-2 molecule, staining of normal bone marrow myeloblasts,
promyelocytes, and myelocytes, but neither monocytes nor most
polymorphonuclear cells, was demonstrated. By two-color flow cytometric
analysis, bcl-2 was evidenced in CD33+ and CD33+/CD34+ myeloid cells as
well as in the more primitive CD33-/CD34+ population. The leukemic cell
lines HL-60, KG1, GM-1, and K562 were bcl-2 positive together with 11 of 14
acute myeloid leukemias (AML) and three of three chronic myeloid leukemias
(CML) in blast crises; six of seven CML were negative. Among
myelodysplastic cases, augmentation of the bcl-2 positive myeloblastic
compartment was found in refractory anemia with excess of blasts (RAEB) and
in transformation (RAEB-t). Western blots of myeloid leukemias and control
lymphocytes extracts evidenced an anti- bcl-2 immunoreactive band of the
expected size (26 Kd). Moreover, the HL-60 and KG1 cell lines, both
positive for the bcl-2 protein, exhibited the appropriate size bcl-2 mRNA
(7.5 Kb). These findings clearly indicate that the bcl-2 gene is operative
in myeloid cells and that the anti-bcl-2 MoAb identifies its product and
not a cross- reactive epitope. Induction of HL-60 differentiation toward
the monocytic and granulocytic pathways was accompanied by a marked
decrease in bcl-2 mRNA and protein levels; bivariate flow cytometric
analysis showed that the fraction becoming bcl-2 negative was in the G1
phase of the cell cycle. These data establish that the bcl-2 proto-
oncogene is expressed on myeloid cells and their progenitors and is
regulated in a differentiation-linked manner.
Volume 79,
Issue 5,
pp. 1291-1298,
03/01/1992
Copyright © 1992 by The American Society of Hematology
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