Newly diagnosed acute lymphoblastic leukemia in China (II): prognosis related to genetic abnormalities in a series of 1091 cases
Newly diagnosed acute lymphoblastic leukemia in China (II): prognosis related to genetic abnormalities in a series of 1091 cases
复制标题
DOI：
10.1038/leu.2012.23
复制
发表时间：
2012-07-01
期刊：
影响因子：
11.4
通讯作者：
Chen, S-J
中科院分区：
文献类型：
--
作者：
Mi, J-Q;Wang, X.;Chen, S-J
细胞遗传学异常的分子表征不仅提供了对白血病发生机制的见解，而且还导致建立针对这些异常的新的治疗策略，从而进一步改善患者的预后。我们分析了1091例新诊断的中国急性淋巴细胞白血病（ALL）患者的预后，并探讨了大量细胞遗传学/分子异常对预后的影响。据证实，在B-和T-ALL的设置，预后呈负相关的年龄报告。对于儿童T-ALL患者，也有记录表明HOX 11表达代表了与成人患者一样的有利预后因素。根据细胞遗传学/分子风险对儿童B- ALL病例进行分层时，我们确定CRLF 2过表达为中等风险标志物，IKZF 1基因的Ik 6变异为高风险标志物。我们还发现Ik 6变异和CRLF 2过表达在决定Ph阴性患者的预后中具有重要作用，这可能是未来指导ALL治疗的有用标志物，另一方面，酪氨酸激酶抑制剂可逆转Ph阳性ALL患者的命运。
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.