bcl-2 proto-oncogene expression in normal and neoplastic human myeloid cells.

Journal article

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.

Authors: Delia, D; Aiello, A; Soligo, D; Fontanella, E; Melani, C

• Publication status: Published
• Journal: Blood
• Volume: 79
• Issue: 5
• Pages: 1291-1298
• Publication date: 1992-03-01
• EISSN: 1528-0020
• ISSN: 0006-4971
• Language: English
• Keywords: Immunohistochemistry; Gene Expression; Leukemia, Myeloid, Acute; Proto-Oncogene Proteins; Tumor Cells, Cultured; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Anemia, Refractory, with Excess of Blasts; Blotting, Western; Gene Expression Regulation, Neoplastic; Granulocytes; RNA, Messenger; Proto-Oncogene Proteins c-bcl-2; Leukemia, Promyelocytic, Acute; Flow Cytometry; Leukemia; Bone Marrow; Cell Differentiation; Humans