Constitutive expression of IL‐1β, M‐CSF and c‐fms during the myeloid blastic phase of chronic myelogenous leukaemia

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Abstract
During the myeloid blast crisis (BC) of chronic myelogenous leukaemia (CML) non‐random additional chromosome abnormalities occur in over 80% of patients. However, these cytogenetic changes have been reported to precede the clinical signs of CML‐BC by several months to years suggesting that other biological events may participate in the multistep process of acute transformation of CML. The autocrine production of growth factors has been recently shown to occur in several haematological malignancies and particularly in acute myeloblastic leukaemia (AML). In the present report we demonstrate that IL‐1β gene is expressed in almost all cases of CML in myeloid blast crisis. The secretion of IL‐1 from CML blasts in culture supernatants was confirmed in all five of the patients we studied. A high proportion of cases showed constitutive expression of the M‐CSF gene and many of the same patients often had a simultaneous co‐expression of the proto‐oncogene c‐fms which encodes for the M‐CSF receptor. After exposure of leukaemic cells to phorbol myristate acetate (PMA), release of M‐CSF protein was documented in three of five patients studied. No significant interleukin‐3 (IL‐3), granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) or granulocyte colony‐stimulating factor (G‐CSF), was detected in these patients demonstrating that a different pattern of growth factors secretion exist in AML and CML, where distinct molecular events are likely involved in the control of leukaemic proliferation.

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