Gene expression profiling of acute myeloid leukemia with translocation t(8;16)(p11;p13) and MYST3-CREBBP rearrangement reveals a distinctive signature with a specific pattern of HOX gene expression
Gene expression profiling of acute myeloid leukemia with translocation t(8;16)(p11;p13) and MYST3-CREBBP rearrangement reveals a distinctive signature with a specific pattern of HOX gene expression
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DOI：
10.1158/0008-5472.can-05-4601
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发表时间：
2006-07-15
期刊：
影响因子：
11.2
通讯作者：
Campo, Elias
中科院分区：
文献类型：
--
作者：
Camos, Mireia;Esteve, Jordi;Campo, Elias
T(8；16)(p11；p13)易位的急性髓系白血病(AML)是一种罕见的白血病亚型，具有独特的临床生物学特征。这种易位导致MYST3(MoZ)和CREBBP(CBP)基因的融合，可能导致粒单核细胞前体转录程序的紊乱。尽管如此，它的基因表达谱尚不清楚。我们使用寡核苷酸U133A阵列(Affymetrix)分析了23例AML患者的基因表达谱，其中包括3例经分子证实的MYST3-CREBBP融合基因。MYST3-CREBBP病例聚集在一起，明显区别于PML-RARα、RUNX1-Runx1t1和CBFβ-MYH11重排样本。在另一组40例患者中，包括7例MYST3-CREBBP AML患者，用低密度阵列分析了根据高密度阵列研究中差异表达选择的46个基因的相对表达。因此，催乳素(PRL)和原癌基因RET等基因在MYST3-CREBBP样本中特异性高表达，而CCND2、STAM和STAM等基因在该AML类别中差异低表达。有趣的是，MYST3-CREBBP AML表现出HOX表达的特征模式，HOXA9、HOXA10和辅因子MEISI上调，其他同源框基因显著下调。该文件过表达了Flt3、HOXA9、Meis1、AKR7A2、.CHD3和APBA2部分类似于有MLL重排的AML。综上所述，本研究显示了MYST3-CREBBP AIM独特的基因表达谱，具有RET和PRL的过表达以及HOX基因表达的特殊模式。
Acute myeloid leukemia (AML) with translocation t(8;16)(p11;p13) is an infrequent leukemia subtype with characteristic clinicobiological features. This translocation leads to fusion of MYST3 (MOZ) and CREBBP (CBP) genes, probably resulting in a disturbed transcriptional program of a myelomonocytic precursor. Nonetheless, its gene expression profile is unknown. We have analyzed the gene expression profile of 23 AML patients, including three with molecularly confirmed MYST3-CREBBP fusion gene, using oligonnucleotide U133A arrays (Affymetrix). MYST3-CREBBP cases clustered together and clearly differentiated from samples with PML-RAR alpha, RUNX1-RUNX1T1, and CBF beta-MYH11 rearrangements. The relative expression of 46 genes, selected according to their differential expression in the high-density array study, was analyzed by low-density arrays in an additional series of 40 patients, which included 7 MYST3-CREBBP AML cases. Thus, genes such as prolactin (PRL) and protooncogene RET were confirmed to be specifically overexpressed in MYST3-CREBBP samples whereas genes such as CCND2, STAM, and STAM were differentially underexpressed in this AML category. Interestingly, MYST3-CREBBP AML exhibited a characteristic pattern of HOX expression, with up-regulation of HOXA9, HOXA10, and cofactor MEISI and marked down-regulation of other homeobox genes. This lrofile, with overexpression of FLT3, HOXA9, MEIS1, AKR7A2,. CHD3, and APBA2, partially resembles that of AML with MLL rearrangement. In summary, this study shows the distinctive gene expression profile of MYST3-CREBBP AIM, with overexpression of RET and PRL and a specific pattern of HOX gene expression.