Genome profiling of acute myelomonocytic leukemia: alteration of the MYB locus in MYST3-linked cases.
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.
Murati
A
A
Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Marseille, France.
Gervais
C
C
Carbuccia
N
N
Finetti
P
P
Cervera
N
N
Adélaïde
J
J
Struski
S
S
Lippert
E
E
Mugneret
F
F
Tigaud
I
I
Penther
D
D
Bastard
C
C
Poppe
B
B
Speleman
F
F
Baranger
L
L
Luquet
I
I
Cornillet-Lefebvre
P
P
Nadal
N
N
Nguyen-Khac
F
F
Pérot
C
C
Olschwang
S
S
Bertucci
F
F
Chaffanet
M
M
Lessard
M
M
Mozziconacci
M-J
MJ
Birnbaum
D
D
D015704:CD4 Antigens / Q000235:genetics; D055028:Comparative Genomic Hybridization; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D020570:Genes, myb / Q000235:genetics*; D015894:Genome, Human; D051548:Histone Acetyltransferases / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics
D015704:CD4 Antigens; D018398:Homeodomain Proteins; D020598:Proto-Oncogene Proteins c-myb; C088144:HoxA protein; D051548:Histone Acetyltransferases; C108712:KAT6A protein, human