Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MLL (ALL1, Htrx, HRX), which is located on chromosome band 11q23, frequently is rearranged in patients with therapy-related acute myeloid leukemia who previously were treated with DNA topoisomerase II inhibitors. In this study, we have identified a fusion partner of MLL in a 10-year-old female who developed therapy-related acute myeloid leukemia 17 months after treatment for Hodgkin's disease. Leukemia cells of this patient had a t(11;17)(q23;q25), which involved MLL as demonstrated by Southern blot analysis. The partner gene was cloned from cDNA of the leukemia cells by use of a combination of adapter reverse transcriptase-PCR, rapid amplification of 5' cDNA ends, and BLAST database analysis to identify expressed sequence tags. The full-length cDNA of 2.8 kb was found to be an additional member of the septin family, therefore it was named MSF (MLL septin-like fusion). Members of the septin family conserve the GTP binding domain, localize in the cytoplasm, and interact with cytoskeletal filaments. A major 4-kb transcript of MSF was expressed ubiquitously; a 1.7-kb transcript was found in most tissues. An additional 3-kb transcript was found only in hematopoietic tissues. By amplification with MLL exon 5 forward primer and reverse primers in MSF, the appropriately sized products were obtained. MSF is highly homologous to hCDCrel-1, which is a partner gene of MLL in leukemias with a t(11;22)(q23;q11.2). Further analysis of MSF may help to delineate the function of MLL partner genes in leukemia, particularly in therapy-related leukemia.
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PMID:MSF (MLL septin-like fusion), a fusion partner gene of MLL, in a therapy-related acute myeloid leukemia with a t(11;17)(q23;q25). 1033 4

The t(11;17) has been described in patients with acute myeloid leukemia (AML), and the AF17 gene was previously cloned as a fusion partner of the MLL gene in t(11;17)(q23;q21)-AML. We analyzed one patient with de novo AML and one with therapy-related AML with t(11;17)(q23;q25) and identified the AF17q25 gene on chromosome 17q25, a putative septin family gene, fused with MLL. AF17q25 encoded at least three kinds of proteins [type I (568 a.a.), type II (594 a.a.), and type III (574 a.a.)] that contained two kinds of different amino acid sequences at the COOH terminus. The MLL-AF17q25 fusion transcript consisted of type I AF17q25 transcript. The AF17q25 protein is homologous to septin family proteins, including H5, NEDD5, CDC10, and hCDCrel, which is one of the fusion partners of MLL in t(11;22)(q23;q11)-AML. These results suggest that AF17q25 and hCDCrel might define a new septin family particularly involved in the pathogenesis of 11q23-associated leukemia.
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PMID:AF17q25, a putative septin family gene, fuses the MLL gene in acute myeloid leukemia with t(11;17)(q23;q25). 1048 69

An expression sequence tag identified in a screen for genes upregulated by retinoic acid induced neuronal differentiation of the human teratocarcinoma cell line Ntera2/D1 was found in close genomic proximity to a region of high sequence homology to the septin subfamily of GTPase genes. We could show that the tag corresponds to the 3' untranslated region of this novel gene named septin 3 and cloned three isoforms A (2191 bp), B (4378 bp), and C (1896 bp) from human Ntera2/D1 cDNA. We present the genomic localization and organization on chromosome 22q13.2, a chromosomal hot spot for translocations implicated in leukemia. Interestingly, MSF the closest paralog of septin 3 is a fusion partner in a therapy-related acute myeloid leukemia. Quantitative PCR confirmed the upregulation of the putative septin by neuronal differentiation and northern blotting showed only one band corresponding to sep3B with a neurospecific expression pattern in adult human tissues.
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PMID:Human septin 3 on chromosome 22q13.2 is upregulated by neuronal differentiation. 1132 66

There are a limited number of reports of acute myeloid leukemia (AML) with t(10;11)(q22;q23). We showed that the MLL gene on 11q23 was fused to the LCX (leukemia-associated protein with a CXXC domain) gene on 10q22 in a de novoadult AML-M2 with trilineage dysplasia having t(10;11)(q22;q23). LCX consisted of at least 12 exons and was predicted to encode a 2136-amino-acid protein with an estimated molecular mass of 235.3 kDa. The LCX protein had a zinc-binding CXXC domain that MLL also contains within a methyltransferase domain, three nuclear localization signals, an alpha-helical coiled-coil region, and two homologous regions to CG2083 proteins of Drosophila melanogaster. We found approximately 12-, 9.5-, and 7.5-kb transcripts of LCX. Expression of the 7.5-kb transcript was detected in fetal heart, lung, and brain, and in adult skeletal muscle, thymus, and ovary. Expression of the 9.5-kb transcript was detected in fetal lung and brain and in adult ovary. Expression of the 12-kb transcript was detected in fetal heart and brain and in adult thymus and ovary. LCX was expressed in 8 of 22 leukemic cell lines, but not in EBV-induced normal B-cell lines. The MLL-LCX fusion protein lacked a CXXC domain of LCX, but retained an alpha-helical coiled-coil region at the COOH terminus, similar to MLL-SEPTING, MLL-CDCREL1, MLL-AF1p/Eps15, and MLL-AF6, which suggests that these fusion proteins are involved in the pathogenesis of 11q23-associated leukemia through similar mechanisms.
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PMID:LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23). 1212 44