| t(4;11) leukemias display addiction to MLL-AF4 but not to AF4-MLL. | |
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MedLine Citation:
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PMID: 20869771 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Ashish R Kumar; Qing Yao; Quanzhi Li; Thien A Sam; John H Kersey |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-09-25 |
Journal Detail:
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Title: Leukemia research Volume: 35 ISSN: 1873-5835 ISO Abbreviation: Leuk. Res. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-03-07 Completed Date: 2011-05-17 Revised Date: 2012-09-19 |
Medline Journal Info:
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Nlm Unique ID: 7706787 Medline TA: Leuk Res Country: England |
Other Details:
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Languages: eng Pagination: 305-9 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA. ashish.kumar@cchmc.org |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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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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