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MOZ is fused to p300 in an acute monocytic leukemia with t(8;22)
M Chaffanet1, L Gressin, C Preudhomme
1Laboratoire d'Oncologie Moléculaire, INSERM U119, Marseille, France.
Abstract:
We report on the fusion of the monocytic leukemia zinc finger protein (MOZ) gene to the adenoviral E1A-associated protein p300 (p300) gene in acute monocytic leukemia M5 associated with a t(8;22)(p11;q13) translocation. We studied two patients with double-color fluorescence in situ hybridization (FISH) using the yeast artificial chromosome 176C9 and the bacterial artificial chromosome clone H59D10 specific to the MOZ and p300 genes, respectively. Both probes were split in the patients' chromosome metaphase cells, and the two derivative chromosomes were each labeled with both probes. We showed by Southern blot the rearrangement of the MOZ gene, and cloned the fusion transcripts in one patient carrying the t(8;22) by reverse transcription-polymerase chain reaction using MOZ- and p300-specific primers. Both fusion transcripts were expressed. This result defines a novel reciprocal translocation involving two acetyltransferases, MOZ and p300, resulting in an abnormal transcriptional co-activator that could play a critical role in leukemogenesis.
Insights
A novel gene fusion between the monocytic leukemia zinc finger protein (MOZ) and adenoviral E1A-associated protein p300 (p300) was identified in acute monocytic leukemia. This MOZ-p300 fusion creates an abnormal co-activator, potentially driving leukemogenesis.
Area of Science:
- Hematology
- Molecular Biology
- Genetics
Background:
- Acute monocytic leukemia (AML M5) is a subtype of leukemia.
- Chromosomal translocations are common in leukemia and can lead to gene fusions.
- The MOZ and p300 genes encode acetyltransferases involved in transcriptional regulation.
Purpose of the Study:
- To investigate a novel gene fusion in acute monocytic leukemia.
- To characterize the molecular consequences of a t(8;22) translocation.
- To identify potential drivers of leukemogenesis.
Main Methods:
- Double-color fluorescence in situ hybridization (FISH) using specific probes for MOZ and p300 genes.
- Southern blot analysis to detect MOZ gene rearrangement.
- Reverse transcription-polymerase chain reaction (RT-PCR) to clone and identify fusion transcripts.
Main Results:
- A reciprocal translocation t(8;22)(p11;q13) was identified in two patients with AML M5.
- FISH analysis confirmed the rearrangement and fusion of MOZ and p300 genes.
- Fusion transcripts involving MOZ and p300 were detected and cloned, indicating their expression.
Conclusions:
- A novel MOZ-p300 gene fusion resulting from the t(8;22) translocation has been identified in acute monocytic leukemia.
- This fusion generates an abnormal transcriptional co-activator.
- The MOZ-p300 fusion protein may play a critical role in the development of leukemia.