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• W1552876488 abstract "Mixed Lineage Leukemia constitutes a heterogeneous category of rare acute leukemias that are characterized by a mixed population of poorly differentiated lymphoid and myeloid progenitor cells. The mixed lineage leukemia (MLL1) gene, also known as HRX or ALL-1, is a frequent site of genetic rearrangements in infant acute leukemias and therapy-related malignancies (Daser and Rabbitts, 2005) and since its discovery (Djabali et al., 1992; Tkachuk et al., 1992; Ziemin-van der Poel et al., 1991), significant progress has been made in understanding its role in human biology and leukemogenesis (Liu et al., 2009; Slany, 2009). Chromosomal abnormalities involving the MLL1 gene include reciprocal chromosomal translocations, internal partial tandem duplications (PTD), and amplifications of unrearranged MLL1 (Dou and Hess, 2008). These chromosomal aberrations are associated with mechanistically distinct gain-of-function phenotypes that may be amenable to targeted therapeutic approaches. However, progress in this area has been impeded by a lack of understanding of the molecular details by which MLL1 translocations, amplifications and PTDs contribute to leukemogenesis. To date, more than 60 MLL1 fusion partners have been described (Krivtsov and Armstrong, 2007), and detailed genetic/biochemical studies have identified several functional domains within chimeric MLL1-fusion proteins that are essential for leukemic transformation (Daser and Rabbitts, 2005; Debernardi et al., 2002; Eguchi et al., 2004; Ernst et al., 2002; Krivtsov and Armstrong, 2007; Lavau et al., 2000; Liu et al., 2009; Luo et al., 2001; Mitterbauer-Hohendanner and Mannhalter, 2004; Mueller et al., 2009; Prasad et al., 1995). Although our understanding of the molecular pathology of MLL1associated leukemias remains incomplete, recent biochemical and structural information is contributing to an evolution of potential treatment strategies from a broadly-based chemotherapeutics approach towards therapies targeted to the underlying molecular pathogenesis of leukemia (Liedtke and Cleary, 2009). This chapter reviews recent advances in our efforts to develop novel MLL1-targeted therapies." @default.
• W1552876488 created "2016-06-24" @default.
• W1552876488 creator A5000379104 @default.
• W1552876488 creator A5080090648 @default.
• W1552876488 date "2011-12-22" @default.
• W1552876488 modified "2023-10-03" @default.
• W1552876488 title "Biochemistry of the Mixed Lineage Leukemia 1 (MLL1) Protein and Targeted Therapies for Associated Leukemia" @default.
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