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【JAMA】与儿童白血病治疗反应相关的遗传变异
CHICAGO – Children with acute lymphoblastic leukemia with certain genetic variations can have a different response to anti-cancer treatment than other patients, according to a study in the January 28 issue of JAMA.
Pediatric acute lymphoblastic leukemia (ALL) cure rates have increased from less than 10 percent in the 1960s to more than 80 percent today, although considerable unexplained individual variability exists in treatment response, according to background information in the article.
Jun J. Yang, Ph.D., of St. Jude Children’s Research Hospital, Memphis, Tenn., and colleagues conducted a study to identify genetic factors that may affect treatment response in ALL. The researchers tested single nucleotide polymorphisms (SNPs; genetic variations) for their association with minimal residual disease (MRD) at the end of initial chemotherapy in two groups (totaling 487 children) treated for newly diagnosed ALL. Patients were enrolled between 1994 and 2006, with the last follow-up in 2006.
The researchers found that there were 102 SNPs associated with MRD in both groups. All 102 SNPs remained significantly associated with MRD after adjustment for race, sex, leukocyte (a type of blood cell) count at diagnosis, age, and ALL subtype. Of the 102 SNPs, 21 were significantly associated with hematologic (blood-related) relapse. Of 102 SNPs, 21 were also associated with antileukemic drug disposition, generally linking MRD eradication with greater drug exposure. The researchers found that a high proportion (63 of 102 SNPs [61.7 percent]) also were associated with early response, relapse risk, or antileukemic drug disposition.
“Although the acquired genetic characteristics of tumor cells play a critical role in drug responsiveness, our results show that inherited genetic variation of the patient also affects effectiveness of anticancer therapy, and that genome-wide approaches can identify novel and yet plausible pharmacogenetic variation. Such variation may be factored into treatment decisions in the future by placing additional emphasis on optimizing drug delivery to overcome host genetic variation, in addition to the current emphasis on tumor genetic variation,” the authors conclude.
据1月28日刊JAMA上的一则研究披露，具有某些遗传变异的急性成淋巴细胞性白血病的患儿与其他的病人相比，他们对抗癌治疗会有不同的反应。
根据文章的背景资料，儿科的急性成淋巴细胞性白血病（ALL）的治愈率已经从1960年代的不到10%增加至如今的80%以上，但是这些病儿对治疗的反应却存在着相当大的且无法解释的个体差异。
St. Jude Children’s Research Hospital, Memphis, Tenn.的Jun J. Yang, Ph.D.及其同僚开展了一项研究，旨在发现可能影响ALL治疗反应的那些遗传因子。研究人员在2组患者（共有487名患儿）的最初化疗结束的时候对他们进行了单核苷酸多态性（SNPs；即遗传变异）测试以期发现它们与微小残留病变（MRD）之间的相关性，这些儿童都被新近诊断患有ALL。这些患者是在1994年至2006年期间被接纳到研究之中的，对他们的最后的随访时间是在2006年。
研究人员发现，在这2组中，有102种SNPs与MRD相关。所有102种SNPs在经过族裔、性别、诊断时淋巴细胞（一种类型的血液细胞）计数、年龄以及ALL亚型的校正之后仍然与MRD具有显著的相关性。在102种SNPs中，有21种与该疾病的血液病学性（即与血液相关的）的复发具有显著的相关性。在102种SNPs中，有21种还与抗白血病的药物处置具有相关性，它们通常会将MRD的根除与更多的药物接触关联在一起。研究人员发现，有很高比例（63/102 SNPs [ 61.7% ]）的SNPs还与早期的反应、复发的风险，或抗白血病药物的处置具有关联性。
文章的作者得出结论：“尽管肿瘤细胞的后天遗传特征在其对药物的反应上起着关键性的作用，但我们的结果显示，患者的先天性遗传变异也会影响抗癌治疗的效果。考量整个基因组的方法会使我们发现新的而且可能的药理遗传学的变异。除了目前强调的肿瘤遗传变异之外，这种变异可能在未来通过格外强调最佳药物传递以克服宿主遗传变异而将其计入决定治疗的因素”。 [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-03-09 13:19
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