Lineage-specific and differentiation-stage-specific gene expression in normal and leukaemic human myeloid cells

One example of each of two approaches to the isolation of molecular hybridization probes and their use for the comparative investigation of gene expression and its control during differentiation of normal and leukaemic leukocytes is described. RNA preparations from the peripheral blood leukocytes of human leukaemias of various types were assayed for the relative abundance of the mRNA homologous with a cellular oncogene, c-myc. All types of leukaemia except chronic lymphatic leukaemia (CLL) showed varying levels of myc-related RNA; the highest concentrations occurred in cell populations in which blast cells predominated. In contrast, a recombinant plasmid (pCG14), isolated from a cDNA recombinant plasmid library that represented polyadenylated RNAs from the peripheral blood leukocytes of a chronic granulocytic leukaemia (CGL), hybridized with an mRNA whose occurrence is diagnostic of CGL leukocytes. This mRNA was also found in normal bone marrow cells; in both bone marrow and in CGL leukocytes, pCG14-homologous RNA occurs only in cells around the myelocyte stage in differentiation. It is suggested that these probes, and others for mRNAs whose occurrence is specific to a particular cell lineage and/or stage in differentiation, detect a new series of potential diagnostic markers. These might usefully supplement existing ones to provide a more detailed, objective subclassification of the leukaemias which could have important implications for diagnosis and therapy.