2 DISTINCT PORTIONS OF LTG19 ENL AT 19P13 ARE INVOLVED IN T(11 19) LEUKEMIA/

We previously isolated cDNA clones, MLL-a and MLL-b, derived from the 11q23 breakpoint region and detected gene rearrangements with MLL-b cD NA in infantile leukemia cell lines with 11q23 abnormalities. We also showed chimeric mRNAs between MLL and genes on partner chromosomes suc h as 4q21 and 19p13. In the present study, we isolated overlapping MLL cDNA clones of 11 kb and demonstrated that MLL-a and MLL-b were deriv ed from the same gene, MLL/ALL-1/HRX. Northern analysis with an MLL cD NA probe detected different signals in t(11;19) cell lines, one being sized 10 kb in two cell lines, KOCL-33 and KOCL-44, and the other bein g 9.2 kb in the cell line, KOPN-1. To elucidate the molecular basis fo r the heterogeneity, we isolated cDNA clones of a translocation-associ ated gene on chromosome 19, LTG19, as well as chimeric cDNAs from KOPN -1. Northern analysis with LTG19 cDNA demonstrated the identical gene, encoding serine/proline rich 559 amino acid polypeptide, to be involv ed in all three cell lines. Sequence comparison revealed that the LTG1 9 portion of the predicted chimeric protein of KOPN-1 was fused in fra me and contained the C-terminal 189 amino acids. This was shorter by 3 66 amino acids than those of KOCL-33 and KOCL-44, also fused in frame. Reverse transcriptase-PCR analysis demonstrated complex chimeric mRNA s in cell lines and leukemia samples. Although a chimeric mRNA of KOPN -1 type was rare, its presence suggested that the shared C-terminal po rtion of 189 amino acids of LTG19 contains important signal(s) for mal ignant transformation.