Abl protein kinase abrogates the response of multipotent haemopoietic cells to the growth inhibitor macrophage inflammatory protein-1 alpha

Oncogene
G WarkA D Whetton

Abstract

The clonogenic cells of chronic myeloid leukaemia (CML), unlike normal haemopoietic progenitor cells, are resistant to the growth inhibitory effects of the chemokine macrophage inflammatory protein-1 alpha (MIP-1alpha). CML is also relatively resistant to chemotherapy and the disease is difficult to cure using conventional therapeutic routes. CML is associated with increased abl oncogene protein tyrosine kinase (PTK) activity. Here, we have tested the hypothesis that these aberrant responses to MIP-1alpha and the relative resistance to chemotherapy are directly related to this increased abl PTK activity in primitive haemopoietic cells. To do this we have expressed a temperature sensitive abl PTK in a growth factor dependent, multipotent stem cell line (FDCP-Mix) in which growth is normally suppressed by MIP-1alpha. In FDCP-Mix cells expressing the ts v-abl PTK and grown at the restrictive temperature for PTK activity the cells were relatively sensitive to cytotoxic agents such as cytosine arabinoside and 5-fluorouracil but MIP-1alpha could induce growth inhibition and confer some degree of protection from these agents. At the permissive temperature for abl PTK, the cells were relatively resistant to cytotoxic drugs and MIP-1alp...Continue Reading

Citations

Sep 5, 2002·The Journal of Experimental Medicine·Andrzej PtasznikAlan M Gewirtz
Oct 30, 2013·The Journal of Experimental Medicine·Tomohisa BabaNaofumi Mukaida
Jul 10, 1999·Current Opinion in Hematology·U R Osarogiagbon, P B McGlave
Aug 23, 2017·International Journal of Molecular Sciences·Naofumi MukaidaTomohisa Baba
May 29, 2002·Oncogene·Jiang Zhu, Stephen G Emerson
Jan 1, 2014·Molecular & Cellular Oncology·Tomohisa Baba, Naofumi Mukaida

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