Abstract
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.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis*
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Blotting, Western
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Cell Cycle
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Cell Proliferation
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Chromosomes, Human, Pair 11 / genetics*
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Chromosomes, Human, Pair 4 / genetics*
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / genetics*
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Histone-Lysine N-Methyltransferase
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Humans
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Leukemia / genetics*
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Leukemia / pathology
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Myeloid-Lymphoid Leukemia Protein / antagonists & inhibitors
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Myeloid-Lymphoid Leukemia Protein / genetics*
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Nuclear Proteins / antagonists & inhibitors
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Nuclear Proteins / genetics*
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Oncogene Proteins, Fusion / antagonists & inhibitors
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Oncogene Proteins, Fusion / genetics*
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RNA, Messenger / genetics
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RNA, Small Interfering / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Transcriptional Elongation Factors
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Translocation, Genetic / genetics*
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Tumor Cells, Cultured
Substances
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DNA-Binding Proteins
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KMT2A protein, human
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MLL-AF4 fusion protein, human
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Nuclear Proteins
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Oncogene Proteins, Fusion
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RNA, Messenger
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RNA, Small Interfering
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Transcriptional Elongation Factors
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Myeloid-Lymphoid Leukemia Protein
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AFF1 protein, human
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Histone-Lysine N-Methyltransferase