Expression of dominant-negative Ikaros isoforms and associated genetic alterations in Chinese adult patients with leukemia
Expression of dominant-negative Ikaros isoforms and associated genetic alterations in Chinese adult patients with leukemia
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中国成年白血病患者显性失活 Ikaros 亚型的表达及相关基因改变
DOI：
10.1007/s00277-012-1415-4
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发表时间：
2012-07-01
影响因子：
3.5
通讯作者：
Ge, Zheng
中科院分区：
文献类型：
--
作者：
Liu, Ping;Lin, ZhongKun;Ge, Zheng
显性阴性Ikaros亚型在白血病的发病机制中具有重要作用，目前主要在儿童患者中进行研究，而在中国成人患者中的研究较少。我们检测了339例中国成人白血病患者，并与以往的研究结果进行了比较，发现DN亚型在Ph+ALL和慢性粒细胞白血病淋巴/混合急变中过度表达。我们证实IKZF 1基因外显子4-7的缺失与Ikaros 6（Ik 6）的产生有关。此外，我们观察到DN亚型表达与BCR-ABL 1转录水平动态一致，与Ph+ALL患者3个月内复发率较高或诱导化疗反应较差相关，与ALL患者高白色血细胞、原始细胞、CD 34阳性细胞和延迟达到完全血液学缓解相关。总之，本研究为在成人ALL（尤其是Ph+ALL患者）的评价中整合异常Ikaros亚型（尤其是Ik 6和Ik 10）提供了依据。
Dominant-negative (DN) Ikaros isoforms, having important roles in pathogenesis of leukemia, are mainly studied in pediatric patients, but little is known about Chinese adult patients. We examined 339 Chinese adult patients with leukemia and demonstrated the different findings between our results and those in several previous studies showing that DN isoforms overexpressed in Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) and lymphoid/mixed blast crisis of chronic myelogenous leukemia. We confirmed that deletion ofIKZF1gene exons 4–7 is responsible for the generation of Ikaros 6 (Ik6). Moreover, we observed that expression of DN isoforms was dynamically consistent with BCR-ABL1 transcript levels, associated with higher incidence of relapse within 3 months or poor response to induction chemotherapy in Ph+ALL, correlated with high white blood cell, blast cells, CD34 positive cells, and delayed achieving complete hematological remission in ALL patients. In conclusion, this study provides a rationale for the integration of aberrant Ikaros isoforms, notably Ik6 and Ik10, in the evaluation of adult ALL, particularly in Ph+ALL patients.