Jain Preetesh, Kantarjian Hagop, Patel Keyur P, Gonzalez Graciela Nogueras, Luthra Rajyalakshmi, Kanagal Shamanna Rashmi, Sasaki Koji, Jabbour Elias, Romo Carlos Guillermo, Kadia Tapan M, Pemmaraju Naveen, Daver Naval, Borthakur Gautam, Estrov Zeev, Ravandi Farhad, O'Brien Susan, Cortes Jorge
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Internal Medicine, University of Texas Medical School at Houston, Houston, TX;
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;
Blood. 2016 Mar 10;127(10):1269-75. doi: 10.1182/blood-2015-10-674242. Epub 2016 Jan 4.
The most common breakpoint cluster region gene-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL) transcripts in chronic myeloid leukemia (CML) are e13a2 (b2a2) and e14a2 (b3a2). The impact of the type of transcript on response and survival after initial treatment with different tyrosine kinase inhibitors is unknown. This study involved 481 patients with chronic phase CML expressing various BCR-ABL transcripts. Two hundred patients expressed e13a2 (42%), 196 (41%) expressed e14a2, and 85 (18%) expressed both transcripts. The proportion of patients with e13a2, e14a2, and both achieving complete cytogenetic response at 3 and 6 months was 59%, 67%, and 63% and 73%, 81%, and 82%, respectively, whereas major molecular response rates were 27%, 49%, and 50% at 3 months, 42%, 67%, and 70% at 6 months, and 55%, 83%, and 76% at 12 months, respectively. Median (international scale) levels of transcripts e13a2, e14a2, and both at 3 months were 0.2004, 0.056, and 0.0612 and at 6 months were 0.091, 0.0109, and 0.0130, respectively. In multivariate analysis, e14a2 and both predicted for optimal responses at 3, 6, and 12 months. The type of transcript also predicted for improved probability of event-free (P = .043; e14a2) and transformation-free survival (P = .04 for both). Compared to e13a2 transcripts, patients with e14a2 (alone or with coexpressed e13a2) achieved earlier and deeper responses, predicted for optimal European Leukemia Net (ELN) responses (at 3, 6, and 12 months) and predicted for longer event-free and transformation-free survival.
慢性髓性白血病（CML）中最常见的断裂点簇集区基因-阿贝尔森鼠白血病病毒癌基因同源物1（BCR-ABL）转录本是e13a2（b2a2）和e14a2（b3a2）。不同酪氨酸激酶抑制剂初始治疗后，转录本类型对反应和生存的影响尚不清楚。本研究纳入了481例表达各种BCR-ABL转录本的慢性期CML患者。200例患者表达e13a2（42%），196例（41%）表达e14a2，85例（18%）同时表达这两种转录本。e13a2、e14a2以及两种转录本均表达的患者在3个月和6个月时达到完全细胞遗传学反应的比例分别为59%、67%、63%以及73%、81%、82%，而主要分子反应率在3个月时分别为27%、49%、50%，6个月时分别为42%、67%、76%，12个月时分别为55%、83%、76%。转录本e13a2、e14a2以及两种转录本均表达的患者在3个月时的中位（国际标准）水平分别为0.2004、0.056、0.0612，6个月时分别为0.091、0.0109、0.0130。多变量分析显示，e14a2以及两种转录本均表达预测在3个月、6个月和12个月时反应最佳。转录本类型还预测无事件生存（P = 0.043；e14a2）和无转化生存（两者均为P = 0.04）概率提高。与e13a2转录本相比，e14a2（单独或与共表达的e13a2一起）患者实现反应更早、更深，预测欧洲白血病网（ELN）反应最佳（在3个月、6个月和12个月时），并预测无事件生存和无转化生存时间更长。
