Expression of BCR-ABL in M1 myeloid leukemia cells induces differentiation without arresting proliferation
- Author(s)
- Cambier, N; Zhang, Y; Vairo, G; Kosmopoulos, K; Metcalf, D; Nicola, NA; Elefanty, AG;
- Details
- Publication Year 1999-01-14,Volume 18,Issue #2,Page 343-352
- Journal Title
- ONCOGENE
- Publication Type
- Journal Article
- Abstract
- The mechanism leading to the expanding population of maturing myeloid cells which characterises chronic myeloid leukemia (CML) remains obscure. Because of its ability to mimic the proliferative and cell survival functions of hematopoietic growth factors, me hypothesized that the oncogene activated in CML, BCR-ABL, might also influence differentiation. To test this hypothesis, nle examined the effects of expressing BCR-ABL on the myeloid differentiation of murine M1 leukemic cells, which cease dividing and differentiate into macrophages in the presence of the cytokines leukemia inhibitory factor (LIF) or interleukin (IL)-6, We found that BCR-ABL induced macrophage differentiation in M1 cells, accompanied by increased expression of macrophage cell surface markers and the acquisition of phagocytic ability. Interestingly, clones of M1 cells which expressed BCR-ABL remained in cell cycle and were refractory to the growth inhibition and apoptosis induced by IL-6 or LIF in parental M1 cells. These cells also expressed inappropriately high levels of c-MYC mRNA for their degree of differentiation, which may have been important in maintaining cellular proliferation. These data suggest that BCR-ABL can stimulate both differentiation and proliferation and that these characterisitics may contribute to the phenotype observed in CML.
- Publisher
- STOCKTON PRESS
- Keywords
- CHRONIC MYELOGENOUS LEUKEMIA; CONSTITUTIVE C-MYC; INHIBITORY FACTOR; TYROSINE KINASE; MONOCLONAL-ANTIBODY; SCAVENGER RECEPTOR; CYCLIN D1; V-ABL; ERYTHROLEUKEMIA-CELLS; ONCOGENE EXPRESSION
- Publisher's Version
- https://doi.org/10.1038/sj.onc.1202302
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1999-01-14 12:00:00