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Adenoviral E1A-associated protein p300 is involved in acute myeloid leukemia with t(11;22)(q23;q13)
1Department of Pediatrics, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Abstract:
p300, which was originally cloned as a nuclear binding target of the adenovirus E1A oncoprotein, forms a family with cyclic-AMP response element binding protein (CREB)-binding protein (CBP). p300/CBP are considered to be transcriptional coactivators that connect the basal transcriptional machinery to various DNA-binding transcriptional factors. p300/CBP are implicated in both cell differentiation and regulation of cell-cycle. We identify here that the p300 gene is fused to the MLL gene and that in-frame MLL-p300 fusion protein is generated in acute myeloid leukemia (AML) with t(11; 22)(q23; q13). These findings suggest that the basis for the leukemogenesis of t(11; 22)-AML is the inability of p300 to regulate cell-cycle and cell differentiation after fusion with MLL.
Insights
The p300 gene fuses with the MLL gene in acute myeloid leukemia (AML) with t(11; 22) chromosomal translocation. This MLL-p300 fusion protein disrupts cell cycle and differentiation, leading to leukemogenesis.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- p300 and CREB-binding protein (CBP) are transcriptional coactivators involved in cell differentiation and cell-cycle regulation.
- p300 was initially identified as a nuclear binding target of the adenovirus E1A oncoprotein.
- These proteins link the basal transcriptional machinery to DNA-binding transcription factors.
Purpose of the Study:
- To investigate the role of p300 in acute myeloid leukemia (AML) with a specific chromosomal translocation.
- To identify the molecular mechanism underlying leukemogenesis in t(11; 22)-AML.
Main Methods:
- Gene fusion analysis in AML patient samples.
- Identification of the specific MLL-p300 fusion protein.
Main Results:
- The study identified a fusion between the p300 gene and the MLL gene.
- An in-frame MLL-p300 fusion protein is generated in acute myeloid leukemia (AML) carrying the t(11; 22)(q23; q13) translocation.
- This fusion event leads to the generation of a chimeric MLL-p300 protein.
Conclusions:
- The MLL-p300 fusion protein is implicated in the development of acute myeloid leukemia (AML) with t(11; 22) translocation.
- Leukemogenesis in this AML subtype is attributed to the impaired ability of the fused p300 to regulate cell-cycle and cell differentiation.
- The findings highlight the critical role of p300 in maintaining normal cellular processes and its disruption in cancer development.