Patkar Nikhil, Subramanian P G, Tembhare Prashant, Mandalia Sneha, Chaterjee Gaurav, Rabade Nikhil, Kodgule Rohan, Chopra Karishma, Bibi Asma, Joshi Swapnali, Chaudhary Shruti, Mascerhenas Russel, Kadam-Amare Pratibha, Narula Gaurav, Arora Brijesh, Banavali Shripad, Gujral Sumeet
Hematopathology Laboratory, Tata Memorial Centre, Mumbai, Maharashtra, India.
Department of Cancer Cytogenetics, Tata Memorial Centre, Mumbai, Maharashtra, India.
Indian J Pathol Microbiol. 2017 Apr-Jun;60(2):209-213. doi: 10.4103/IJPM.IJPM_466_16.
Copy number alterations (CNA) have been described in childhood precursor B-lineage acute lymphoblastic leukemia (B-ALL) which in conjunction with chromosomal abnormalities drive leukemogenesis. There is no consensus on the clinical incorporation of CNA in B-ALL. An integrated genomic classification (IGC) has been proposed which includes CNA and cytogenetics.
We correlated this IGC with immunophenotypic minimal residual disease (MRD) as well as other standard criteria for 245 patients of B-ALL such as National Cancer Institute (NCI) risk, D+8 prednisolone response, cytogenetics, and ploidy status.
MRD was detectable in 81 patients (33.1%). The most common abnormalities were seen in CDKN2A/B (25.7%) followed by PAX5(20%), ETV6(16.7%), IKZF1(15.5%), Rb1(5.3%), BTG (3.3%), EBF1(2.0%), and PAR1(0.8%). On integrating CNA into the IGC, 170 patients (69.4%) were classified into good genomic risk (GEN-GR) whereas 75 (30.6%) belonged to the poor genomic risk (GEN-PR) category. The IGC showed a significant correlation with MRD and NCI risk. The presence of CNA predicted MRD clearance in intermediate cytogenetics group.
These data seem to indicate that in addition to cytogenetics, CNA should be incorporated into routine clinical testing and risk algorithms for B-ALL. The IGC is of prognostic relevance and offers an additional avenue for prognostication and risk-adapted therapy.
儿童前体B淋巴细胞系急性淋巴细胞白血病（B-ALL）中已发现拷贝数改变（CNA），其与染色体异常共同驱动白血病发生。关于CNA在B-ALL临床应用中的共识尚未达成。已提出一种综合基因组分类（IGC），其中包括CNA和细胞遗传学。
我们将这种IGC与免疫表型微小残留病（MRD）以及245例B-ALL患者的其他标准标准进行了关联，如美国国立癌症研究所（NCI）风险、D+8泼尼松反应、细胞遗传学和倍性状态。
81例患者（33.1%）可检测到MRD。最常见的异常见于CDKN2A/B（25.7%），其次是PAX5（20%）、ETV6（16.7%）、IKZF1（15.5%）、Rb1（5.3%）、BTG（3.3%）、EBF1（2.0%）和PAR1（0.8%）。将CNA纳入IGC后，170例患者（69.4%）被归类为良好基因组风险（GEN-GR），而75例（30.6%）属于不良基因组风险（GEN-PR）类别。IGC与MRD和NCI风险显著相关。CNA的存在预测了中间细胞遗传学组中MRD的清除。
这些数据似乎表明，除细胞遗传学外，CNA应纳入B-ALL的常规临床检测和风险算法中。IGC具有预后相关性，为预后评估和风险适应性治疗提供了另一条途径。
