Significance of AF4-MLL reciprocal fusion in t(4;11) leukemias?

Department of Pathology, University of Michigan, 1301 Catherine St, Ann Arbor, MI 48109, USA.
Leukemia research (Impact Factor: 2.35). 10/2010; 35(3):299-300. DOI: 10.1016/j.leukres.2010.09.015
Source: PubMed
9 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Genetic mutations and gross structural defects in the DNA sequence permanently alter genetic loci in ways that significantly disrupt gene function. In sharp contrast, genes modified by aberrant epigenetic modifications remain structurally intact and are subject to partial or complete reversal of modifications that restore the original (i.e. non-diseased) state. Such reversibility makes epigenetic modifications ideal targets for therapeutic intervention. The epigenome of cancer cells is extensively modified by specific hypermethylation of the promoters of tumor suppressor genes relative to the extensive hypomethylation of repetitive sequences, overall loss of acetylation, and loss of repressive marks at microsatellite/repeat regions. In this review, we discuss emerging therapies targeting specific epigenetic modifications or epigenetic modifying enzymes either alone or in combination with other treatment regimens. The limitations posed by cancer treatments elicit unintended epigenetic modifications that result in exacerbation of tumor progression are also discussed. Lastly, a brief discussion of the specificity restrictions posed by epigenetic therapies and ways to address such limitations is presented.
    No preview · Article · Jul 2013 · Cancer Treatment Reviews
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chromosomal translocations of the human mixed-lineage leukemia (MLL) gene have been analyzed for more than 20 yr at the molecular level. So far, we have collected about 80 direct MLL fusions (MLL-X alleles) and about 120 reciprocal MLL fusions (X-MLL alleles). The reason for the higher amount of reciprocal MLL fusions is that the excess is caused by 3-way translocations with known direct fusion partners. This review is aiming to propose a solution for an obvious problem, namely why so many and completely different MLL fusion alleles are always leading to the same leukemia phenotypes (ALL, AML, or MLL). This review is aiming to explain the molecular consequences of MLL translocations, and secondly, the contribution of the different fusion partners. A new hypothesis will be posed that can be used for future research, aiming to find new avenues for the treatment of this particular leukemia entity. © The Korean Society for Laboratory Medicine This is an Open Access article distributed under the terms of the Creative Commns Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Full-text · Article · Mar 2016 · Annals of Laboratory Medicine