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[Cancer Research 62, 4075-4080, July 15, 2002]
© 2002 American Association for Cancer Research


Molecular Biology and Genetics

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)1

Ryoichi Ono, Tomohiko Taki, Takeshi Taketani, Masafumi Taniwaki, Hajime Kobayashi and Yasuhide Hayashi2

Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, 113-8655 [R. O., T. Taki., T. Take., Y. H.], Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8655 [M. T.]; and Fourth Department of Internal Medicine, Obihiro Kousei Hospital, Obihiro, 080-0016 [H. K.], Japan

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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