IDENTIFICATION OF MLL AND CHIMERIC MLL GENE-PRODUCTS INVOLVED IN 11Q23 TRANSLOCATION AND POSSIBLE MECHANISMS OF LEUKEMOGENESIS BY MLL TRUNCATION

11q23 chromosome aberrations are frequently observed in infantile as w eb as therapy-related leukemias, The target gene at 11q23, MLL, is dis rupted by the translocation and becomes fused to various translocation partner genes such as AF4/FEL, LTG9/AF9 and LTG19/ENL, The resulting chimeric mRNAs are fused in frame and have been predicted to encode le ukemia-specific chimeric proteins, In the present study, we raised ant ibodies against MLL, LTG9 and LTG19 and demonstrated that MLL and chim eric MLL-LTG9 and MLL-LTG19 products are synthesized in vivo and are l ocalized in the nuclei, using immunofluorescence and cell fractionatio n studies, The truncated N-terminal portion of the MLL product common to the various types of 11q23 translocation was also localized in the nuclei in a similar fashion, Murine 32Dc13 cells stably expressing the truncated N-terminal MLL protein exhibited an inhibition of different iation and a growth advantage following stimulation by granulocyte-col ony stimulating factor, although the IL-3 dependency was not significa ntly changed in comparison to the parental cells, These results sugges t that the N-terminal portion common to various MLL-chimeric products plays an important role in leukemogenesis.