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]
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]
A Murati
- Fonction : Auteur
P Finetti
- Fonction : Auteur
- PersonId : 753338
- IdHAL : pascal-finetti
- ORCID : 0000-0002-2674-3123
F Bertucci
- Fonction : Auteur
- PersonId : 1209245
- ORCID : 0000-0002-2425-9362
- IdRef : 161524885
M Chaffanet
- Fonction : Auteur
- PersonId : 753068
- IdHAL : max-chaffanet
- ORCID : 0000-0002-2344-1488
Résumé
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.