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- trolled by the balance between these genes. We sugges that these chromosomes also carry genes that control the mahgnancy of these cells.The development of an experimental system for the in vitro induction of differentiation in various types of white-blood cells (1-7), has made it possible to study the control mechanisms that regulate the differentiation of these cells and the blocks that can occur in leukemia and nonmalignant diseases (6,(8)(9)(10)(11)(12)(13). It has been shown that some myeloid leukemic cells can be induced to differentiate normally by incubation with the differentiation inducing protein MGI (macrophage and granulocyte inducer) (6, 8, 9) and that there are other myeloid leukemic cells with different blocks in differentiation (10, 12). Clones of one type of cell (MGI+) can be induced by MGI to form Fc and C3 rosettes, which is a stage in the differentiation of myeloid cells, whereas clones of another type of cell (MGI-) cannot be induced by MGI for the surface changes that result in the formation of rosettes. The MGI+ clones can be divided into two types, one of which (MGI+D+), was also induced by MGI to form mature macrophages and granulocytes, and the other (MGI+D-) was induced to form Fc and C3 rosettes but not mature cells. The MGI-clones were all D-and could not be induced to form rosettes or mature cells (10, 12).The clonal origin and inheritance of the differences in inducibility by MGI suggested that there may be genetic differences between the different cell types and that it may be possible to map the chromosome location of the genes involved (14). The clones used, even those that had been in culture for more than a year, still had a diploid or near-diploid modal chromosome number, so that these cells appear to be particularly favorable for mapping the genes that control differentiation and malignancy. It MATERIALS AND METHODSCells and Cell Culture. Ten clones of myeloid leukemic cells were used in the present study. Two clones (11 and 12) were MGI+D+; two clones (2 and 4) were MGI+D-; and these four clones were isolated (9) from a myeloid leukemic cell line in culture obtained from a spontaneous myeloid leukemia in a female SL mouse (15). The other six clones (1, 6, 7, 8, 10, and 15) were separately cloned MGI-myeloid leukemic cell lines established in Vitro from the first or second transplant generation of six independently arising myeloid leukemias after irradiation of female SJL/J mice with x-rays (16). The lymphoid leukemias studied were also obtained after irradiation o...

The oncogenic potential of an activated Hox-2.4 homeobox gene in mouse fibroblasts.

“…1 (2). This deletion is the most common chromosome aberration in mouse myeloid leukemia cells, and it is not present in WEHI-3B leukemic cells (2,6).…”

Retroviral insertions in the murine His-1 locus activate the expression of a novel RNA that lacks an extensive open reading frame.

“…5). This is supported by the fact that genomic primers located 5 T''TAAA sequence and the end of the current cDNA sequence (Fig. 5 [underlined area]) amplified a specific product from reverse-transcribed cDNA (data not shown).…”

Phenotypic effect correlating with loss of a novel tumor suppressor gene: towards cloning by complementation

“…7 The pattern of synteny with human chromosomes is complex in the vicinity of the deletion, 37 so that prediction of the location of the human homologue is difficult. Meanwhile, the mouse model has allowed us to take the dual approaches of fine mapping of the gene, as we have done in parallel work (Ref.…”

“…3 Although the undifferentiated parent line is transformed by Abelson leukemia virus, the continued rapid growth of differentiated macrophage-like subclones seems to depend on the acquisition of tumorigenic karyotypic abnormalities, 4 viz trisomy of chromosomes (chrs) 5 or 12, 5 translocation of chr 16 6 or deletion of chr2. [7][8][9][10] The chr2 aberrations have been known for 20 years to contribute to myelogenous leukemia. 7 We have confirmed the interpretation of others that deletion of a putative TSG on this chromosome is an important tumorigenic event.…”

“…[7][8][9][10] The chr2 aberrations have been known for 20 years to contribute to myelogenous leukemia. 7 We have confirmed the interpretation of others that deletion of a putative TSG on this chromosome is an important tumorigenic event. 4,11 We have chosen to compare our chr2-deleted and non-deleted clonally related lines to help identify and clone the TSG lost in this deletion.…”