Topography, Clinical, and Genomic Correlates of 5q Myeloid Malignancies Revisited
Topography, Clinical, and Genomic Correlates of 5q Myeloid Malignancies Revisited
复制标题
DOI：
10.1200/jco.2011.36.1824
复制
发表时间：
2012-04-20
影响因子：
45.3
通讯作者：
Maciejewski, Jaroslaw P.
中科院分区：
文献类型：
--
作者：
Jerez, Andres;Gondek, Lukasz P.;Maciejewski, Jaroslaw P.
目的染色体5 q的间质性缺失在急性髓细胞白血病（AML）和骨髓增生异常综合征（MDS）中很常见，提示该区域在疾病表型和克隆进化中的致病作用。单核苷酸多态性阵列（SNP-A）核型分析的更高水平的分辨率可用于发现隐藏的异常并精确地定义基因组病变的地形特征，从而允许更准确的临床相关性。155例临床注释良好的恶性髓系疾病患者。结果我们在1例中的142例（12%）中发现了染色体5 q缺失，155例患者中有4例（0.35%）为单亲二体节段（UPD）。涉及5 q的着丝粒和端粒末端缺失的患者具有更具侵袭性的疾病表型和额外的染色体病变。不涉及5 q的着丝粒或端粒末端的病变并非5 q综合征所独有，但可能与其他侵袭性较低的MDS形式有关。此外，较大的5 q缺失与del（17 p）或del 17 p相关。在31 33例del（5 q）AML，无论是涉及着丝粒和/或端粒区或杂合突变NPM 1或MAML 1位于5q35.ConclusionOur的结果表明，在5 q的受影响的区域的程度确定的临床特征，可以进一步修改的杂合突变存在于端粒的极端。
PurposeInterstitial deletions of chromosome 5q are common in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), pointing toward the pathogenic role of this region in disease phenotype and clonal evolution. The higher level of resolution of single-nucleotide polymorphism array (SNP-A) karyotyping may be used to find cryptic abnormalities and to precisely define the topographic features of the genomic lesions, allowing for more accurate clinical correlations.Patients and MethodsWe analyzed high-density SNP-A karyotyping at diagnosis for a cohort of 1,155 clinically well-annotated patients with malignant myeloid disorders.ResultsWe identified chromosome 5q deletions in 142 (12%) of 1,155 patients and uniparental disomy segments (UPD) in four (0.35%) of 1,155 patients. Patients with deletions involving the centromeric and telomeric extremes of 5q have a more aggressive disease phenotype and additional chromosomal lesions. Lesions not involving the centromeric or telomeric extremes of 5q are not exclusive to 5q- syndrome but can be associated with other less aggressive forms of MDS. In addition, larger 5q deletions are associated with either del(17p) or UPD17p. In 31 of 33 patients with del(5q) AML, either a deletion involving the centromeric and/or telomeric regions or heterozygous mutations in NPM1 or MAML1 located in 5q35 were present.ConclusionOur results suggest that the extent of the affected region on 5q determines clinical characteristics that can be further modified by heterozygous mutations present in the telomeric extreme.