Immune responses to chronic myeloid leukaemia

The negative impact of donor marrow T lymphocyte depletion on relapse of chronic myeloid leukaemia (CML) following bone marrow transplantation strongly suggests that the leukaemia is particularly susceptible to immune regulation. The immune response to CML may be mediated by major histocompatibility (MHC) locus unrestricted natural killer and lymphokine activated killer cells, or by MHC-restricted CD4 and CD8 lymphocytes. Interaction with the leukaemia is both by direct cell-contact cytotoxicity, and indirectly via cytokines and growth factors. T4 and T8 lymphocytes recognize a spectrum of minor histocompatibility antigens on the leukaemia cell which may be non-specific, leading to graft-versus-leukaemia and graft-versus-host reactions, or present only on myeloid cells leading to a tissue restricted response. The possibility that the P210 protein derived from the BCR/ABL fusion gene on chromosome 22 leads to the presentation via MHC molecules of leukaemia-specific peptide antigens is currently under investigation. Developments in understanding the immune response to CML open up the possibility of developing leukaemia-specific immunotherapy strategies.