bcr-abl, the hallmark of chronic myeloid leukaemia in man, induces multiple haemopoietic neoplasms in mice.
The chromosome translocation forming the hybrid bcr-abl gene is thought to be the initiating event in chronic myeloid leukaemia (CML) and some cases of acute lymphoblastic leukaemia. To assess the impact of bcr-abl upon haemopoiesis, lethally irradiated mice were reconstituted with bone marrow cells enriched for cycling stem cells and infected with a bcr-abl bearing retrovirus. The mice developed several fatal diseases with abnormal accumulations of macrophage, erythroid, mast and lymphoid cells, and marked strain differences in disease distribution and kinetics. Some mice exhibited more than one neoplastic cell type and, in some instances, these were clonally related, indicating that a progenitor or stem cell had been transformed. While classical CML was not observed, the macrophage tumours were accompanied by a mild CML-like syndrome, probably due to myeloid growth factor production by tumour cells. The erythroid and mast cell diseases were rarely transplantable, in contrast to the macrophage tumours and lymphomas, but all disease types displayed limited clonality. These results establish that bcr-abl confers a proliferative advantage on diverse haemopoietic cells but complete transformation probably involves additional genetic changes.
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
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D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008223:Lymphoma / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000235:genetics*; D009857:Oncogenes; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012190:Retroviridae / Q000235:genetics*; D014162:Transfection
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007377:Interleukin-3; D012313:RNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA; D016044:Fusion Proteins, bcr-abl