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

A Murati (1, 2) , C Gervais (3) , N Carbuccia (1, 2) , P Finetti (1, 2) , N Cervera (1, 2) , J Adélaïde (1, 2) , S Struski (3) , E Lippert (4) , F Mugneret (5) , I Tigaud (6) , D Penther (7) , C Bastard (7) , B Poppe (8) , F Speleman (8) , L Baranger (9) , I Luquet (10) , P Cornillet-Lefebvre (10) , N Nadal (11) , F Nguyen-Khac (12) , C Pérot (13) , S Olschwang (1, 2) , F Bertucci (1, 2) , M Chaffanet (1, 2) , M Lessard (3) , M-J Mozziconacci (1, 2) , D Birnbaum (1, 2)

1 CRCM - Centre de Recherche en Cancérologie de Marseille
2 IPC - Institut Paoli-Calmettes
3 Hôpital de Hautepierre [Strasbourg]
4 Hôpital Haut-Lévêque [CHU Bordeaux]
5 CHU Dijon
6 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
7 CLCC Henri Becquerel - Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen
8 Centrum voor Medische Genetica
9 CHU Angers - Centre Hospitalier Universitaire d'Angers
10 Hôpital Maison Blanche
11 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
12 CHU Pitié-Salpêtrière [AP-HP]
13 CHU Saint-Antoine [AP-HP]

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.

Domaines: Cancer

A Murati, C Gervais, N Carbuccia, P Finetti, N Cervera, et al.. Genome profiling of acute myelomonocytic leukemia: alteration of the MYB locus in MYST3-linked cases. Leukemia, 2009, 23 (1), pp.85-94. ⟨10.1038/leu.2008.257⟩. ⟨hal-03634349⟩