Document Detail


t(4;11) leukemias display addiction to MLL-AF4 but not to AF4-MLL.
MedLine Citation:
PMID:  20869771     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The most frequent MLL-gene rearrangement found in leukemia is a reciprocal translocation with AF4 on chromosome 4 resulting in the formation of the MLL-AF4 and the AF4-MLL fusion genes. The oncogenic role of MLL-AF4 is documented but the significance of the reciprocal product - AF4-MLL in leukemia is less clear. In the human leukemia cell lines - RS4;11 and SEMK2-M1, both of which express MLL-AF4 and AF4-MLL, we knocked down the expression of AF4-MLL using siRNA. Loss of AF4-MLL had no effect on the growth of either RS4;11 or SEMK2-M1 cells. Furthermore, in SEMK2-M1 cells there were no changes in cell cycle or apoptosis with loss of AF4-MLL. In contrast, knockdown of MLL-AF4 significantly inhibited growth of both RS4;11 and SEMK2-M1. Additionally, in SEMK2-M1 cells, loss of MLL-AF4 led to G2/M cell cycle arrest and increased apoptosis. Overall, these results demonstrate that in t(4;11) leukemia, the MLL-AF4 fusion protein is critical for leukemia cell proliferation and survival while the AF4-MLL fusion product is dispensable.
Authors:
Ashish R Kumar; Qing Yao; Quanzhi Li; Thien A Sam; John H Kersey
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-09-25
Journal Detail:
Title:  Leukemia research     Volume:  35     ISSN:  1873-5835     ISO Abbreviation:  Leuk. Res.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-07     Completed Date:  2011-05-17     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  7706787     Medline TA:  Leuk Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  305-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA. ashish.kumar@cchmc.org
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MeSH Terms
Descriptor/Qualifier:
Apoptosis*
Blotting, Western
Cell Cycle
Cell Proliferation
Chromosomes, Human, Pair 11 / genetics*
Chromosomes, Human, Pair 4 / genetics*
DNA-Binding Proteins / antagonists & inhibitors,  genetics*
Humans
Leukemia / genetics*,  pathology
Myeloid-Lymphoid Leukemia Protein / antagonists & inhibitors,  genetics*
Nuclear Proteins / antagonists & inhibitors,  genetics*
Oncogene Proteins, Fusion / antagonists & inhibitors,  genetics*
RNA, Messenger / genetics
RNA, Small Interfering / genetics
Reverse Transcriptase Polymerase Chain Reaction
Translocation, Genetic / genetics*
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
K08 CA122191-03/CA/NCI NIH HHS; K08-CA122191/CA/NCI NIH HHS; R01 CA087053-09/CA/NCI NIH HHS; R01-CA087053/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/MLL protein, human; 0/MLL-AF4 fusion protein, human; 0/Nuclear Proteins; 0/Oncogene Proteins, Fusion; 0/RNA, Messenger; 0/RNA, Small Interfering; 149025-06-9/Myeloid-Lymphoid Leukemia Protein; 150826-18-9/AFF1 protein, human
Comments/Corrections

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