DataSheet_1_Gene Deletions and Prognostic Values in B-Linage Acute Lymphoblastic Leukemia.pdf

Although pediatric-like treatment regimen has remarkably improved the survival rates of adults with acute lymphoblastic leukemia (ALL), the outcome of some adult patients is still poor owing to adverse genetic features. These molecular abnormalities, especially gene deletions, may be considered for the prognosis assessment for adult patients with ALL. In this study, using multiplex ligation-dependent probe amplification (MLPA) method, gene deletions were analyzed in from 211 adult B-ALL patients treated in our center. The data showed that 68.2% (144/211) adult B-ALL patients carried gene deletions, and the frequency is much higher in Ph+B-ALL patients. IKZF1 gene deletion is the most common gene deletion in adult B-ALL, followed by CDKN2A/B deletion. In Ph-B-ALL patients, the overall survival of patients with gene deletions is inferior to that of patients without any gene deletions. More obviously, patients with IKZF1 or CDKN2A/B deletion had a worse prognosis, whereas, allogeneic hematopoietic stem cell transplantation could improve OS in patients with IKZF1 deletion, but not in patients with CDKN2A/B deletion. Moreover, the outcome of Ph-B-ALL patients with double deletion of IKZF1and CDKN2A/B may be much worse than that of patients with IKZF1 or CDKN2A/B alone. Minimal residual disease (MRD) was also analyzed together with gene deletions and demonstrated that gene deletions have a negative impact on survival only in MRD positive Ph-B-ALL patients. In conclusion, gene deletions are closely related with the prognosis of adult Ph-B-ALL patients.

尽管类儿童治疗方案已显著提升成人急性淋巴细胞白血病（acute lymphoblastic leukemia, ALL）患者的生存率，但部分成人患者因不良遗传特征仍预后不佳。此类分子异常，尤其是基因缺失，可用于成人ALL患者的预后评估。本研究采用多重连接依赖性探针扩增（multiplex ligation-dependent probe amplification, MLPA）技术，对本中心收治的211例成人B细胞型急性淋巴细胞白血病（B-ALL）患者的基因缺失情况进行了分析。结果显示，68.2%（144/211）的成人B-ALL患者存在基因缺失，且费城染色体阳性B细胞型急性淋巴细胞白血病（Ph+B-ALL）患者的基因缺失检出率更高。其中，IKZF1基因缺失是成人B-ALL中最常见的基因缺失类型，其次为CDKN2A/B缺失。在费城染色体阴性B细胞型急性淋巴细胞白血病（Ph-B-ALL）患者中，存在基因缺失者的总生存期（overall survival, OS）显著差于无基因缺失者。更明确的是，携带IKZF1或CDKN2A/B缺失的患者预后更差；而异基因造血干细胞移植可改善IKZF1缺失患者的总生存期，但对CDKN2A/B缺失患者无此获益。此外，同时存在IKZF1与CDKN2A/B双缺失的Ph-B-ALL患者，其预后较仅携带IKZF1或CDKN2A/B单缺失者更差。本研究同时分析了微小残留病（minimal residual disease, MRD）与基因缺失的关联，结果表明，仅在MRD阳性的Ph-B-ALL患者中，基因缺失才会对生存产生负面影响。综上，基因缺失与成人Ph-B-ALL患者的预后密切相关。