The Synergistic Effect of MEIS1 with HOXB7 or with HOXD8 in Leukemia Induction.

To confirm the synergistic effect of MEIS1 with HOXB7 or with HOXD8, MEIS1 was inserted into the IRES-Cherrypicker MSCV retroviral vector (Clontech) to visualize the MEIS1-expressing cells by surface staining of the Cherrypicker marker protein. As in cDNA library, HOX gene was expressed from MSCV-IRES-GFP retroviral vector. The bone marrow cell transduction and transplantation was done as described in Materials and Method except that mixtures of retroviral supernatants of MEIS1/HOXD8 or MEIS1/HOXB7 were used for infection instead of cDNA library supernatant. A. Co-operation of MEIS1 and HOXB7 in leukemia induction. Co-transduction of bone marrow cells and subsequent transplantation of the transduced cells into host mice induced leukemia in the recipients within 60 days (n = 5). Most of the leukemic cells co-express the MEIS1 and HOX genes, and the cells are of myeloid phenotype. MEIS1 or HOXB7alone did not induce leukemia for more than six months (n = 5). B. Co-operation of MEIS1 and HOXD8 in leukemia induction. Co-transduction of bone marrow cells and subsequent transplantation of the transduced cells into host mice induced leukemia in the recipients within 60 days (n = 5). As shown in the figure, MEIS1 or HOXD8 alone did not induce leukemia for more than six months (n = 5).