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Expression of BCR – ABL in M1 myeloid leukemia cells induces differentiation without arresting proliferation

Oncogene volume 18, pages 343–352 (1999)Cite this 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, we hypothesized that the oncogene activated in CML, BCR – ABL, might also influence differentiation. To test this hypothesis, we 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.

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Acknowledgements

We thank Dr C Scott for assistance with phagocytic assays and labelled-LDL uptake experiments. S Olding and D Berry provided expert assistance with the preparation of figures and Dr CG Begley critically read the manuscript. This work was supported in part by the Association pour la Recherche contre le Cancer (NC), the Carden Fellowship Fund (DM), an Australian Research Council Queen Elizabeth II fellowship and an AMRAD postdoctoral award (GV), the Australian Federal Government Cooperative Research Centres Program (YZ) and the Lions Special Fellowship of the AntiCancer Council of Victoria (AGE), the National Health and Medical Research Council, Canberra and a grant from the National Institutes of Health, CA22556 (DM).

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Authors and Affiliations

  1. The Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Centre for Cellular Growth Factors, PO Royal Melbourne Hospital, 3050, Victoria, Australia

    N Cambier, Y Zhang, G Vairo, K Kosmopoulos, D Metcalf, N A Nicola & A G Elefanty

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  1. N Cambier
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Cambier, N., Zhang, Y., Vairo, G. et al. Expression of BCR – ABL in M1 myeloid leukemia cells induces differentiation without arresting proliferation. Oncogene 18, 343–352 (1999). https://doi.org/10.1038/sj.onc.1202302

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