Chromosome mapping of the genes that control differentiation and malignancy in myeloid leukemic cells

Abstract

The chromosome banding pattern has been analyzed in clones of mouse myeloid leukemic cells that differ in their ability to be induced to differentiate by the protein inducer MGI (macrophage and granulocyte inducer). None of the clones had a completely normal diploid banding pattern. The clones studied were either MGI+ (that can be induced to form Fc and C3 rosettes), a stage in the differentiation of myeloid cells, or MGI- (that cannot be induced to form these rosettes). All six cultured clones of MGI- cells from myeloid leukemias independently produced in six separate animals showed a loss of a piece of one chromosome 2 and this abnormal chromosome was maintained in leukemias derived from the cultured cells. This loss was not found in MGI+ clones or lymphoid leukemias. Five MGI+ mutants, derived from an MGI- clone with a loss of a piece of one chromosome 2, one normal chromosome 12, and two translocated chromosomes 12, maintained the abnormal chromosome 2 but lost either the one normal or one of these translocated chromosome 12. These results indicate that chromosomes 2 and 12 carry genes that control the differentiation of myeloid leukemic cells and that inducibility by MGI is controlled by the balance between these genes. We suggest that these chromosomes also carry genes that control the malignancy of these cells.