Role in growth regulation of cytokines and cytokine receptors in acute lymphoblastic leukaemia expressing myeloid markers

Abstract

The biological roles of cytokines and cytokine receptors were examined in acute lymphoblastic leukaemia cells expressing myeloid antigens (My+ ALL). Interleukin-3 (IL-3), granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), and low molecular-weight B-cell growth factor (LW-BCGF) could induce DNA synthesis in certain cases of My+ ALL. Whereas in My- ALL the stimulatory effects were shown only with LW-BCGF. Acute myelogenous leukaemia (AML) cells were activated with multiple cytokines including interleukin-1 (IL-1), IL-3, G-CSF and GM-CSF. Specific receptors for IL-1 and IL-3 were strongly expressed on both My+ and My- ALL cells. These receptors, however, were weakly detectable on AML cells. Additionally we studied the production of tumour necrosis factor-alpha and IL-1 by leukaemic blasts and found that distinct amounts of both cytokines were released from My+ ALL cells and AML cells, but not from My- ALL cells. The profiles of cytokines and cytokine receptors expressed by My+ ALL showed both similarities and differences to those in My- ALL or AML. The proliferation of My+ ALL cells was dependent on multiple cytokines that would regulate growth and maturation in a lineage-restricted fashion. These data suggested that My+ ALL cells might originate from uncommitted haematopoietic precursor cells coexpressing features of both lymphoid and myeloid lineages.