Prognostic impact of IKZF1 deletion in adults with common B-cell acute lymphoblastic leukemia.
Prognostic impact of IKZF1 deletion in adults with common B-cell acute lymphoblastic leukemia.
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DOI：
10.1186/s12885-016-2300-7
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发表时间：
2016-04-11
期刊：
影响因子：
3.8
通讯作者：
Ruan GR
中科院分区：
文献类型：
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作者：
Yao QM;Liu KY;Gale RP;Jiang B;Liu YR;Jiang Q;Jiang H;Zhang XH;Zhang MJ;Chen SS;Huang XJ;Xu LP;Ruan GR
询问IKZF1缺失对成人常见B细胞急性淋巴细胞白血病治疗结果的影响。对165例成人中常见的B细胞ALL进行了IKZF1缺失和bcr/abl检测。采用多重RQ-PCR、多重荧光聚合酶链式反应、序列分析和多重连接依赖的探针扩增(MLPA)检测IKZF1基因的缺失。用荧光定量聚合酶链式反应检测bcr/abl。所有受试者都接受了化疗，一些人还接受了同种异体移植和酪氨酸激酶抑制剂。多因素分析确定IKZF1基因缺失与无复发死亡率(NRM)、累积复发发生率(CIR)、无白血病生存率(LFS)和生存率的其他变量之间的关系。在获得完全缓解的受试者中，IKZF1缺失者的5年无复发死亡率相似(11%[2-20%]比16%[4-28%]；P = 0.736)，5年累计复发率(CIR)更高(55%[35-76%]比25%[12-38%]；P = 0.004)，更差的5年无白血病生存率(33%[16-52%]比59%[42-73%])；P = 0.012)和生存率(48%[33-62%]vs.75%[57-86%]；P = 0.002)。在多因素分析中，IKZF1缺失与更高的复发(相对风险[RR]=2.7，[1.4-5.2]；P = 0.002)、更高的治疗失败风险(与LFS相反；RR = 2.1，[1.2-3.6]；P = 0.007)和更高的死亡风险(RR = 2.8，[1.5-5.5]；P = 0.002)相关。在未携带bcr-abl1基因的受试者和仅接受化疗的受试者与接受同种异体移植的受试者中，IKZF1缺失对预后的不利影响更大。在调整了其他预后变量和治疗差异后，IKZF1缺失与患有共同B细胞的成人患者的复发风险更高、LFS和生存率更差独立相关。这些数据表明，IKZF1缺失可能是成人常见B细胞ALL的一个有用的预后变量，特别是在没有bcr-abl1基因的人和那些只接受化疗的人中。移植似乎克服了IKZF1缺失对治疗结果的不利影响，但需要在随机研究中得到证实。该试验于2007年在北京市政府登记(北京市卫生局登记编号：2007-1007)。
Interrogate the impact of IKZF1 deletion on therapy-outcomes of adults with common B-cell acute lymphoblastic leukemia. One hundred sixty-five consecutive adults with common B-cell ALL were tested for IKZF1 deletion and for BCR/ABL. Deletions in IKZF1 were detected using multiplex RQ-PCR, multiplex fluorescent PCR, sequence analysis and multiplex ligation-dependent probe amplification (MLPA). BCR/ABL was detected using RQ-PCR. All subjects received chemotherapy and some also received an allotransplant and tyrosine kinase-inhibitors. Multivariate analyses were done to identify associations between IKZF1 deletion and other variables on non-relapse mortality (NRM), cumulative incidence of relapse (CIR), leukemia-free survival (LFS) and survival. Amongst subjects achieving complete remission those with IKZF1 deletion had similar 5-year non-relapse mortality (NRM) (11 % [2–20 %] vs. 16 % [4–28 %]; P = 0.736), a higher 5-year cumulative incidence of relapse (CIR) (55 % [35–76 %] vs. 25 % [12–38 %]; P = 0.004), and worse 5-year leukemia-free survival (LFS) (33 % [16–52 %] vs. 59 % [42–73 %]; P = 0.012) and survival (48 % [33–62 %] vs. 75 % [57–86 %]; P = 0.002). In multivariate analyses IKZF1 deletion was associated with an increased relapse (relative risk [RR] =2.7, [1.4–5.2]; P = 0.002), a higher risk of treatment-failure (inverse of LFS; RR = 2.1, [1.2–3.6]; P = 0.007) and a higher risk of death (RR = 2.8, [1.5–5.5]; P = 0.002). The adverse impact of IKZF1 deletion on outcomes was stronger in subjects without vs. with BCR-ABL1 and in subjects receiving chemotherapy-only vs. an allotransplant. IKZF1 deletion was independently-associated with a higher relapse risk and worse LFS and survival in adults with common B-cell ALL after adjusting for other prognostic variables and differences in therapies. These data suggest IKZF1 deletion may be a useful prognostic variable in adults with common B-cell ALL, especially in persons without BCR-ABL1 and those receiving chemotherapy-only. Transplants appear to overcome the adverse impact of IKZF1 deletion on therapy-outcomes but confirmation in a randomized study is needed. The trial was registered in 2007 with the Beijing Municipal Government (Beijing Municipal Health Bureau Registration N: 2007–1007).