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

Abstract

The chromosome banding pattern was 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 MGI+ (that can be induced to form Fc and C3 [complement] rosettes), a stage in the differentiation of myeloid cells, or MGI- (that cannot be induced to form these rosettes). All 6 cultured clones of MGI- cells from myeloid leukemias independently produced in 6 animals showed a loss of a piece of 1 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 1 chromosome 2, 1 normal chromosome 12 and 2 translocated chromosomes 12, maintained the abnormal chromosome 2 but lost the 1 normal or 1 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. These chromosomes may also carry genes that control the malignancy of these cells.