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

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Murati, A | Gervais, C | Carbuccia, N | Finetti, P | Cervera, N | Adélaïde, J | Struski, S | Lippert, E | Mugneret, F | Tigaud, I | Penther, D | Bastard, C | Poppe, B | Speleman, F | Baranger, L | Luquet, I | Cornillet-Lefebvre, P | Nadal, N | Nguyen-Khac, F | Pérot, C | Olschwang, S | Bertucci, F | Chaffanet, M | Lessard, M | Mozziconacci, M-J | Birnbaum, D

Edité par CCSD ; Springer Nature -

International audience. 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.

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