Cloning of ELL, a gene that fuses to MLL in a t(11;19)(q23;p13.1) in acute myeloid leukemia.

Thirman, Michael J.; Levitan, Denise; Kobayashi, Hajime; Simon, M. Celeste; Rowley, Janet D.

doi:10.1073/pnas.91.25.12110

Cited by 209 publications

(179 citation statements)

References 26 publications

(23 reference statements)

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“…A sequence homology search revealed that the D40 sequence is the same as that of the AF15q14 gene (Hayette et al, 2000). This gene is a partner that fuses with MLL, an oncogenic gene involved in the development of acute leukaemia (Hunger et al, 1993;Thirman et al, 1994;Hernandez et al, 1995;Dimartino and Cleary, 1999). In contrast to normal tissues, D40 was expressed in all human cancer cell lines examined and in several primary human tumours independently of the types and source of the tumours.…”

Section: Discussionmentioning

confidence: 99%

Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers

et al. 2002

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We found a significant correlation between lung cancer in smokers and the expression of a human gene, D40, predominantly expressed in testis and cancers. In an attempt to clone a novel human gene, we screened a cDNA library derived from a human B cell line and obtained a cDNA clone that we refer to as D40. A search for public databases for sequence homologies showed that the D40 gene is identical to AF15q14. D40 mRNA is predominantly expressed in normal testis tissue. However, this gene is also expressed in various human tumour cell lines and primary tumours derived from various organs and tissues, such as lung cancer. We examined the relationship between D40 expression and clinico-pathological characteristics of tumours in primary lung cancer. D40 expression did not significantly correlate with either histological type or pathological tumour stage. However, D40 expression was observed more frequently in poorly differentiated tumours than in well or moderately differentiated ones. Furthermore, the incidence of D40 expression was significantly higher in tumours from patients who smoke than in those from non-smokers. D40/AF15q14 is the first gene in the cancer/testis family for which expression is related to the smoking habits of cancer patients.

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Section: Discussionmentioning

confidence: 99%

Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers

et al. 2002

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“…Many lines of evidences demonstrate that truncations of MLL are restricted within a 0.9 kb fragment in cDNA and a 8.5 kb fragment in genome DNA in humans (Bernard et al, 1994;Chaplin et al, 1995;Corral et al, 1993;Iida et al, 1993;Mitani et al, 1995;Prasad et al, 1993;Thirman et al, 1993Thirman et al, , 1994Trent et al, 1989;Tse et al, 1995;Yamamoto et al, 1993b). Ten translocation partner genes fused to MLL have been cloned to date, but no common structure has been found (Bernard et al, 1994;Corral et al, 1993;Mitani et al, 1995;Nakamura et al, 1993;Tkachuk et al, 1992;Tse et al, 1995), suggesting that the N-terminal portion of MLL plays an important part in leukemogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…In leukemias with 11q23 translocations, MLL is disrupted and the N-terminal portion, including the AThook motifs and the DNA methyltransferase homology region, is fused to various translocation partner genes, such as AF4/FEL, LTG9/AF9 and LTG19/ENL (Gu et al, 1992;Iida et al, 1993;Morrissey et al, 1993;Nakamura et al, 1993;Tkachuk et al, 1992;Yamamoto et al, 1993a,b). Although more than ten di erent chromosomal translocation partner genes have been identi®ed (Thirman et al, 1993;Trent et al, 1989), no shared common structure has been recognized among the partner gene products (Bernard et al, 1994;Chaplin et al, 1995;Corral et al, 1993;Iida et al, 1993;Mitani et al, 1995;Nakamura et al, 1993;Prasad et al, 1993;Thirman et al, 1994;Tse et al, 1995;Yamamoto et al, 1993b). We previously demonstrated that the chimeric MLL products MLL-LTG9 and MLL-LTG19, as well as MLL-Zf (7), the N-terminal portion common to various chimeric MLL products, localize in nuclei (Joh et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Chimeric MLL products with a Ras binding cytoplasmic protein AF6 involved in t(6;11) (q27;q23) leukemia localize in the nucleus

et al. 1997

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In infantile leukemias and therapy-related leukemias, the MLL gene is frequently found to be disrupted and fused to various translocation partner genes, such as AF4/FEL, LTG9/AF9 and LTG19/ENL as a result of 11q23 translocations. We previously showed that the Nterminal portion common to various chimeric MLL products, as well as to MLL-LTG9 and MLL-LTG19, localizes in the nuclei, and therefore suggested that it might play an important role in leukemogenesis. In the present study, MLL-AF6 chimeric products found in the t(6;11) (q27;q23) translocation were analysed since AF6, a Ras-binding protein, exhibits a di erent subcellular localization from that of LTG9/AF9 and LTG19/ENL. Immuno¯uorescence staining data and cell fractionation analyses demonstrated that MLL-AF6 chimeric products localize in the nuclei despite the fact that AF6 itself localizes in the cytoplasm, con®rming the importance of the nuclear localization of chimeric MLL products. The region in the N-terminal portion of MLL responsible for this nuclear localization was examined and found to be a region containing AT-hook motifs.

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“…U19/Eaf2 shows significant sequence homology to the original family member, Eaf1. ELL was discovered as a fusion partner of MLL in the t(11; 19) (q23; p13.1) chromosomal translocation associated with acute myeloid leukemia (Thirman et al, 1994). ELL binds to RNA polymerase II and acts as a transcription elongation factor whose targeted deletion leads to embryonic lethality in mice (Shilatifard et al, 1996(Shilatifard et al, , 1997aMitani et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

U19/Eaf2 knockout causes lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma and prostatic intraepithelial neoplasia

et al. 2007

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(Eaf2) is a potential human tumor suppressor that exhibits frequent allelic loss and downregulation in high-grade prostate cancer. U19/Eaf2, along with its homolog Eaf1, has been reported to regulate transcriptional elongation via interaction with the eleven-nineteen lysine-rich leukemia (ELL) family of proteins. To further explore the tumor-suppressive effects of U19/Eaf2, we constructed and characterized a murine U19/Eaf2-knockout model. Homozygous or heterozygous deletion of U19/Eaf2 resulted in high rates of lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma and prostate intraepithelial neoplasia. Within the mouse prostate, U19/Eaf2 deficiency enhanced cell proliferation and increased epithelial cell size. The knockout mice also exhibited cardiac cell hypertrophy. These data indicate a role for U19/Eaf2 in growth suppression and cell size control as well as argue for U19/Eaf2 as a novel tumor suppressor in multiple mouse tissues. The U19/Eaf2 knockout mouse also provides a unique animal model for three important cancers: lung adenocarcinoma, B-cell lymphoma and hepatocellular carcinoma.

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Cloning of ELL, a gene that fuses to MLL in a t(11;19)(q23;p13.1) in acute myeloid leukemia.

Abstract: To characterize the functions of MLL fusion transcripts, we cloned the gene that fuses to MLL in the translocation t(11;19)(q23;p13

Cited by 209 publications

References 26 publications

Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers

Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers

Chimeric MLL products with a Ras binding cytoplasmic protein AF6 involved in t(6;11) (q27;q23) leukemia localize in the nucleus

U19/Eaf2 knockout causes lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma and prostatic intraepithelial neoplasia

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