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Leukemia. 2009 Jan;23(1):85-94. doi: 10.1038/leu.2008.257. Epub 2008 Sep 25.

Genome profiling of acute myelomonocytic leukemia: alteration of the MYB locus in MYST3-linked cases.

Author information

1
Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Marseille, France.

Abstract

The t(8;16)(p11;p13) is a rare translocation involved in de novo and therapy-related myelomonocytic and monocytic acute leukemia. It fuses two genes encoding histone acetyltransferases (HATs), MYST3 located at 8p11 to CREBBP located at 16p13. Variant translocations involve other HAT-encoding genes such as EP300, MYST4, NCOA2 or NCOA3. MYST3-linked acute myeloid leukemias (AMLs) share specific clinical and biological features and a poor prognosis. Because of its rarity, the molecular biology of MYST3-linked AMLs remains poorly understood. We have established the genome and gene expression profiles of a multicentric series of 61 M4/M5 AMLs including 18 MYST3-linked AMLs by using array comparative genome hybridization (aCGH) (n=52) and DNA microarrays (n=44), respectively. We show that M4/5 AMLs have a variety of rare genomic alterations. One alteration, a gain of the MYB locus, was found recurrently and only in the MYST3-linked AMLs (7/18 vs 0/34). MYST3-AMLs have also a specific a gene expression profile, which includes overexpression of MYB, CD4 and HOXA genes. These features, reminiscent of T-cell acute lymphoid leukemia (ALL), suggest the targeting of a common T-myeloid progenitor.

PMID:
18818702
DOI:
10.1038/leu.2008.257
[Indexed for MEDLINE]

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