TAILIEUCHUNG - Báo cáo khoa học: Mixed lineage leukemia: roles in human malignancies and potential therapy

The increasing number of chromosomal rearrangements involving the humanMLLgene, in combination with differences in clinical behavior and outcome for MLL-rearranged leukemia patients, makes it necessary to reflect on the cancer mechanism and to discuss potential therapeutic strate-gies. To date, 64 different translocations have been identified at the molecular level. | ễFEBS Journal MINIREVIEW Mixed lineage leukemia roles in human malignancies and potential therapy Rolf Marschalek Biochemistry Chemistry Pharmacy Institute of PharmaceuticalBiology Goethe-University of Frankfurt Main Germany Keywords acute leukemia AF4 AF9 AF10 cancer stem cells ELL ENL MLL MLL fusion proteins signaling Correspondence R. Marschalek Goethe-University of Frankfurt Main Department of Biochemistry Chemistry Pharmacy Institute of Pharmaceutical Biology Biocenter N230 Max-von-Laue-Str. 9 D-60438 Frankfurt Main Germany Fax 49 69 798 29662 Tel 49 69 798 29647 E-mail Received 14 November 2009 revised 7 January 2010 accepted 12 January 2010 The increasing number of chromosomal rearrangements involving the human MLL gene in combination with differences in clinical behavior and outcome for MLL-rearranged leukemia patients makes it necessary to reflect on the cancer mechanism and to discuss potential therapeutic strategies. To date 64 different translocations have been identified at the molecular level. With very few exceptions most of the identified fusion partner genes encode proteins that display no homologies or functional equivalence. Only the most frequent fusion partners AF4 family members AF9 ENL AF10 and ELL are involved in the positive transcription elongation factor b-dependent activation cycle of RNA polymerase II. Biological functions remain to be elucidated for the other fusion partners. This minireview tries to sum up some of the available data and mechanisms identified in leukemic stem and leukemic tumor cells and link this information with the known functions of mixed lineage leukemia and certain mixed lineage leukemia fusion partners. doi Mixed lineage leukemia fusions acute leukemia and the HOX signature Mixed lineage leukemia MLL rearrangements define a small subset of acute leukemia patients including those with therapy-induced secondary leukemias. However unlike many .

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