Genome profiling of acute myelomonocytic leukemia: alteration of the MYB locus in MYST3-linked cases
Genome profiling of acute myelomonocytic leukemia: alteration of the MYB locus in MYST3-linked cases
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DOI：
10.1038/leu.2008.257
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发表时间：
2009-01-01
期刊：
影响因子：
11.4
通讯作者：
Birnbaum, D.
中科院分区：
文献类型：
--
作者：
Murati, A.;Gervais, C.;Birnbaum, D.
t（8; 16）（p11; p13）是一种罕见的易位，发生于原发性和治疗相关的粒单核细胞和单核细胞急性白血病。它融合了两个编码组蛋白乙酰转移酶（HAT）的基因，MYST 3位于8 p11，CREBBP位于16 p13。变异易位涉及其他HAT编码基因，如EP 300、MYST 4、NCOA 2或NCOA 3。MYST 3连锁的急性髓性白血病（AML）具有特定的临床和生物学特征，预后不良。由于其罕见性，MYST 3连锁AML的分子生物学仍然知之甚少。我们分别用阵列比较基因组杂交（aCGH）（n = 52）和DNA微阵列（n = 44）建立了61例M4/M5 AML（包括18例MYST 3连锁AML）的基因组和基因表达谱。我们发现M4/5 AML具有多种罕见的基因组改变。MYB基因座的增加是复发性的，仅在MYST 3连锁的AML中发现（7/18 vs 0/34）。MYST 3-AML还具有特定的基因表达谱，其包括MYB、CD 4和HOXA基因的过表达。这些特征，让人联想到T细胞急性淋巴细胞白血病（ALL），提示靶向共同的T-髓系祖细胞。
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.