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中国新诊断的急性淋巴细胞白血病(II):1091 例系列中与遗传异常相关的预后。

Newly diagnosed acute lymphoblastic leukemia in China (II): prognosis related to genetic abnormalities in a series of 1091 cases.

机构信息

State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Leukemia. 2012 Jul;26(7):1507-16. doi: 10.1038/leu.2012.23. Epub 2012 Feb 2.

Abstract

The molecular characterization of cytogenetic abnormalities has not only provided insights into the mechanisms of leukemogenesis but also led to the establishment of new treatment strategies targeting these abnormalities and thereby further improve the prognosis of patients. We analyzed the prognosis of 1091 Chinese patients with newly diagnosed acute lymphoblastic leukemia (ALL) and explored the prognostic impacts of a large number of cytogenetic/molecular abnormalities. It was demonstrated that, in both B- and T-ALL settings, the prognosis was negatively correlated to the age as reported to date. For childhood T-ALL patients, it was also documented that the HOX11 expression represented a favorable prognostic factor as it was in adult ones. We identified CRLF2 overexpression as an intermediate-risk marker and Ik6 variant of IKZF1 gene as a high-risk one when stratifying pediatric B-ALL cases according to cytogenetic/molecular risks. We also found that Ik6 variant and CRLF2 overexpression had an important role in dictating the prognosis of Ph-negative patients, which may be useful markers in guiding the treatment of ALL in the future, with tyrosine kinase inhibitors on the other hand reversing the fate of Ph-positive ALL patients.

摘要

细胞遗传学异常的分子特征不仅提供了对白血病发生机制的深入了解,还导致了针对这些异常的新治疗策略的确立,从而进一步改善了患者的预后。我们分析了 1091 例新诊断的急性淋巴细胞白血病(ALL)中国患者的预后,并探讨了大量细胞遗传学/分子异常的预后影响。结果表明,在 B 细胞和 T 细胞 ALL 中,与目前报道的情况一样,预后与年龄呈负相关。对于儿童 T-ALL 患者,HOX11 表达也被证明是一个有利的预后因素,与成人一样。当根据细胞遗传学/分子风险对儿科 B-ALL 病例进行分层时,我们将 CRLF2 过表达鉴定为中危标志物,将 IKZF1 基因的 Ik6 变体鉴定为高危标志物。我们还发现 Ik6 变体和 CRLF2 过表达在决定 Ph-阴性患者的预后方面起着重要作用,这可能是未来指导 ALL 治疗的有用标志物,另一方面酪氨酸激酶抑制剂则改变了 Ph-阳性 ALL 患者的命运。

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