Molecular allelokaryotyping of relapsed pediatric acute lymphoblastic leukemia
Molecular allelokaryotyping of relapsed pediatric acute lymphoblastic leukemia
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DOI：
10.3892/ijo_00000290
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发表时间：
2009-06-01
影响因子：
5.2
通讯作者：
Koeffler, H. Phillip
中科院分区：
文献类型：
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作者：
Kawamata, Norihiko;Ogawa, Seishi;Koeffler, H. Phillip
复发的急性淋巴细胞白血病(ALL)细胞往往比原发克隆细胞对治疗更具抵抗力，这可能是由于复发的ALL细胞发生了进一步的基因变化所致。这些获得性基因组异常还没有得到充分的表征。为了检测ALL在复发时的额外基因组改变，我们对14例初诊、缓解和复发的ALL骨髓样本进行了单核苷酸多态性基因组芯片(SNP-CHIP)分析。仅有2例初诊时SNP-芯片显示基因组正常。所有14个病例在复发时都有基因组改变；其中10个病例有额外的基因组异常，在诊断时没有出现。位于22q12.2的Ink4a/ARF基因缺失(2例)或NF2基因缺失(2例)是复发时的获得性基因组改变。在3例患者中检测到正常拷贝数的杂合性丢失[单亲二体(UPD)]，这是复发时的额外基因组改变。有趣的是，最初诊断时发现的一些基因组改变，特别是缺失，在复发时消失，表明复发时的ALL细胞是初诊时的小克隆，并在复发时出现。少数病例初诊时三体转变为UPD(2例)或正常显示基因组(2例)。此外，我们发现PTPRD基因内含子23处的中断是一例额外的基因组异常。综上所述，额外的基因组改变在所有复发中都是非常常见的事件；这些异常是否与治疗耐药有关仍有待进一步研究澄清。
Acute lymphoblastic leukemia (ALL) cells at relapse are frequently more resistant to treatment than primary clones and this may be caused by further genetic changes in the ALL cells at relapse. These acquired genomic abnormalities have not been fully characterized. To examine the additional genomic alterations of ALL at relapse, we performed single nucleotide polymorphism genomic microarry (SNP-chip) analysis on 14 ALL bone marrow samples at initial diagnosis, remission and relapse. Only two cases at initial diagnosis had a normal appearing genome by SNP-chip. All 14 cases had genomic alterations at relapse; and 10 of these had additional genomic abnormalities not present at diagnosis. Deletion of either the INK4A/ARF gene (2 cases) or the NF2 gene (2 cases) at 22q12.2 was an acquired genomic change at relapse. Loss of heterozygosity with normal copy number [uniparental disomy (UPD)] was detected in 3 cases as an additional genomic change at relapse. Interestingly, several genomic alterations, especially deletions, detected at initial diagnosis, disappeared at relapse, suggesting the ALL cells at relapse were minor clones at initial diagnosis and emerged at relapse. For several cases, trisomy at initial diagnosis changed to either UPD (2 cases) or normal appearing genome (2 cases). Further, we found disruption of PTPRD gene occurring at intron 23 as an additional genomic abnormality in one case. In summary, additional genomic changes are very common events in ALL at relapse; whether these abnormalities are associated with resistance to treatment remains to clarified in further studies.