Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene on chromosome 10 at band p12 (AF10), involved in the t(10;11) translocation in acute myeloid leukemia, has been identified and shown to contain conserved zinc finger and leucine zipper domains. These regions are highly homologous to the equivalent regions on AF17, the gene involved in the t(11;17) translocations. A series of adult, childhood, and infant leukemias with either simple or complex versions of the t(10;11) has been examined by Southern analysis and shown to involve rearrangement to the HRX locus. Reverse transcriptase-polymerase chain reaction from either bone marrow or peripheral blood cells showed that HRX sequence was fused to AF10 sequence in all 8 cases and subsequent sequence analysis showed an in-frame fusion between the HRX and AF10 sequence. A consistent feature of these fusions was the juxtaposition of the leucine dimerization motif of AF10 onto the NH2-terminal region of HRX. The published data suggest that a similar conclusion can be drawn about the t(11;17) translocation, implying a critical role for this motif in the chimaeric HRX protein.
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PMID:The t(10;11) translocation in acute myeloid leukemia (M5) consistently fuses the leucine zipper motif of AF10 onto the HRX gene. 766 54

A patient with secondary acute myelomonocytic leukemia after treatment with chronic oral etoposide (VP-16) for lung cancer is reported. The leukemic cells showed a t(9;11)(p22;q23) translocation. Southern blot analysis revealed the rearrangement of the MLL (ALL-1/HRX) gene at 11q23. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a chimeric mRNA between the MLL gene at 11q23 and LTG9 (MLLT3/AF-9) gene at 9p22. The patient was successfully treated with a VP-16 based regimen. This case is instructive in the understanding of the leukemogenesis of VP-16-related leukemias.
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PMID:Acute myelomonocytic leukemia after treatment with chronic oral etoposide: are MLL and LTG9 genes targets for etoposide? 794 64

We previously isolated cDNA clones, MLL-a and MLL-b, derived from the 11q23 breakpoint region and detected gene rearrangements with MLL-b cDNA in infantile leukemia cell lines with 11q23 abnormalities. We also showed chimeric mRNAs between MLL and genes on partner chromosomes such 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 derived from the same gene, MLL/ALL-1/HRX. Northern analysis with an MLL cDNA 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 being 9.2 kb in the cell line, KOPN-1. To elucidate the molecular basis for the heterogeneity, we isolated cDNA clones of a translocation-associated 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 involved in all three cell lines. Sequence comparison revealed that the LTG19 portion of the predicted chimeric protein of KOPN-1 was fused in frame and contained the C-terminal 189 amino acids. This was shorter by 366 amino acids than those of KOCL-33 and KOCL-44, also fused in frame. Reverse transcriptase-PCR analysis demonstrated complex chimeric mRNAs in cell lines and leukemia samples. Although a chimeric mRNA of KOPN-1 type was rare, its presence suggested that the shared C-terminal portion of 189 amino acids of LTG19 contains important signal(s) for malignant transformation.
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PMID:Two distinct portions of LTG19/ENL at 19p13 are involved in t(11;19) leukemia. 837 76