Abo Bibliothek: Guest
Digitales Portal Digitale Bibliothek eBooks Zeitschriften Referenzen und Berichte Forschungssammlungen
Critical Reviews™ in Eukaryotic Gene Expression
Impact-faktor: 2.156 5-jähriger Impact-Faktor: 2.255 SJR: 0.649 SNIP: 0.599 CiteScore™: 3

ISSN Druckformat: 1045-4403
ISSN Online: 2162-6502

Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukaryotGeneExpr.v14.i4.10
20 pages

Mechanisms of Transformation by MLL

Jay L. Hess
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 413b Stellar Chance Laboratories, Philadelphia, PA 19104

ABSTRAKT

Rearrangements of the mixed-lineage leukemia gene MLL1 (MLL, HRX, ALL1), the human homologue of the Drosophila gene trithorax, are associated with aggressive acute leukemias in both children and adults. Transformation by rearranged forms of MLL1, including in-frame fusion proteins, partial tandem duplications, and amplification of MLL1 through upregulation of Hox gene and cofactor expression apparently results in a block in hematopoietic differentiation. MLL1 regulates Hox gene expression via direct promoter binding and histone H3 Lys 4 methylation mediated by the intrinsic methyltransferase activity of the SET domain. Mll1 knockout leads to loss of Hox gene expression, defects in hematopoiesis, and embryonic lethality. A close homologue, MLL2 is amplified in some solid tumors. MLL2 also has histone H3 Lys 4 methyltransferase activity that is dependent on menin, a protein mutated in multiple neoplasia type I (MEN1) and which is required for normal Hox expression. These findings underscore the importance of the MLL histone methyltransferases in development and disease.


Articles with similar content:

EGR-1, The Reluctant Suppression Factor:
Critical Reviews™ in Oncogenesis, Vol.7, 1996, issue 1-2
Dan Mercola, Antonella Calogero, Eileen Adamson, Guiseppe Ragona, Chaoting Liu
MARs of Antigen Receptor and Co-Receptor Genes
Critical Reviews™ in Eukaryotic Gene Expression, Vol.9, 1999, issue 3-4
Richard H. Scheuermann , William T. Garrard
HLA Class I Chromosomal Region, Genes, and Products: Facts and Questions
Critical Reviews™ in Immunology, Vol.14, 1994, issue 2
Philippe Le Bouteiller
Phosphorylation-Based Signaling in Fas Receptor-Mediated Apoptosis
Critical Reviews™ in Immunology, Vol.20, 2000, issue 2
John E. Eriksson, Tim H. Holmstrom
HLA Class I Chromosomal Region, Genes, and Products: Facts and Questions
Critical Reviews™ in Immunology, Vol.37, 2017, issue 2-6
Philippe Le Bouteiller