Abstract
Chromosomal rearrangements of the MLL gene are associated with high-risk infant, pediatric, adult, and therapy-induced acute leukemias. So far, about 80 different direct MLL fusions and about 120 reciprocal MLL fusions have been characterized at the molecular level. The common theme in these leukemia-associated genetic rearrangements is the genetic disruption of the MLL gene. This leads to MLL-X fusion proteins that still bind to nuclear factors (e.g., MEN1, LEDGF), which in turn allow them to target promoters and cause ectopic gene transcription. In addition, the most frequent MLL fusions (MLL-AF4, MLL-AF9, MLL-AF10, and MLL-ENL) are all recruiting the wild-type AF4 multiprotein complex that contains the target proteins P-TEFb, BRD4, and DOT1L. Vice versa, reciprocal X-MLL fusions exhibit a PHD domain (H3K4me3 reader domain), sequester the histone acetyltransferases CREBBP and MOF1 and bear a histone methyltransferase domain at their very C-terminus (SET domain). Except for AF4-MLL, the functional consequences deriving from reciprocal fusion proteins are not very well understood. However, based on our knowledge about the above-mentioned MLL fusions, it is reasonable to inhibit their oncogenic activity in a targeted fashion. Re...Continue Reading
References
Oct 25, 1996·The Journal of Biological Chemistry·N F MarshallD H Price
Dec 16, 1997·Trends in Biochemical Sciences·J L Corden, M Patturajan
Mar 30, 2001·The Journal of Biological Chemistry·Y RamanathanT Pe'ery
Jun 18, 2002·Journal of Biomedical Science·Mario Clemente EstableRobert G Roeder
Jun 29, 2004·Oncogene·Adelheid BursenRolf Marschalek
Nov 30, 2006·Oncogene·A GaussmannR Marschalek
Dec 1, 2006·Human Molecular Genetics·Emmanuelle BitounKay E Davies
May 7, 2008·Trends in Genetics : TIG·Sylvain Egloff, Shona Murphy
Nov 4, 2008·Cancer Cell·Andrei V KrivtsovScott A Armstrong
May 16, 2009·Blood·Yi-Hui LinStefan K Bohlander
Mar 3, 2010·Blood·Adelheid BursenRolf Marschalek
Mar 20, 2010·The FEBS Journal·Rolf Marschalek
Jun 19, 2010·Molecular Biology and Evolution·Pengda LiuArno L Greenleaf
Sep 28, 2010·Nature·Panagis FilippakopoulosJames E Bradner
Dec 2, 2010·British Journal of Haematology·Rolf Marschalek
Jul 12, 2011·Cancer Cell·Scott R DaigleRoy M Pollock
Jul 12, 2011·Cancer Cell·Kathrin M BerntScott A Armstrong
Oct 4, 2011·Nature·Mark A DawsonTony Kouzarides
Nov 5, 2011·Science·Jing-Ping HsinJames L Manley
May 3, 2012·The EMBO Journal·Corinna HintermairDirk Eick
Jul 26, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Belete A DesimmieFrauke Christ
Sep 1, 2012·Blood·Aibin ShiTomasz Cierpicki
Jan 29, 2013·Cell Reports·Adam C WilkinsonThomas A Milne
Apr 12, 2013·Cancer Research·Sarah PicaudStefan Knapp
May 1, 2013·Leukemia·C MeyerR Marschalek
Jun 27, 2013·Blood·Scott R DaigleRoy M Pollock
Sep 11, 2013·Journal of Medicinal Chemistry·Olivier MirguetEdwige Nicodème
Jan 7, 2014·Molecular Cell·Fang CaoYali Dou
Jul 13, 2014·Cancer Letters·K WächterR Marschalek
Aug 2, 2014·Cancer Research·Kateřina CermákováJan De Rijck
Citations
Jun 11, 2016·Hematological Oncology·Daniela R Ney GarciaMaria Luiza Macedo Silva
Feb 10, 2016·Leukemia·U DuffnerP Kidd
Nov 1, 2016·International Journal of Hematology·Weiwei Yang, Patricia Ernst
May 6, 2019·Cancer Science·Yajing ChuWeiping Yuan
Apr 12, 2019·Cytogenetic and Genome Research·Roberto R Capela de MatosMaria Luiza M Silva
Aug 10, 2019·Genes & Development·Christian HurtzMarkus Müschen
Jan 9, 2018·Biomarker Research·Jianchang Yang
Nov 22, 2017·Oncotarget·Jianwu FangJustin Gu
Jul 14, 2018·BioMed Research International·Jiaqi TanJianfeng Zhou
Jun 30, 2019·Journal of Hematology & Oncology·Krzysztof BrzezinkaCarlo Stresemann
Apr 30, 2020·Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms·Subham BasuDebabrata Biswas
Dec 11, 2019·Cancer Cell·Andrei V KrivtsovScott A Armstrong
Oct 11, 2020·EBioMedicine·Gisela Jimenez-DuranSeth L Masters