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Expression of dominant-negative Ikaros isoforms and associated genetic alterations in Chinese adult patients with leukemia

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Abstract

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 of IKZF1 gene 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.

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Acknowledgments

This work was supported by the Jiangsu Province Key Medical Talents (RC2011077), the National Natural Science Foundation of China (30973376, 81070437), the Natural Science Foundation of Jiangsu Province (BK2009442), the Scientific Research Foundation for the Returned Overseas Chinese Scholars, the State Education Ministry (303070158HD10), the China Postdoctoral Science Foundation (20090461134 ), special grade of the financial support from the China Postdoctoral Science Foundation (201003598), the Scientific Research Foundation for the Returned Overseas Chinese Scholars, Nanjing Municipal Bureau of Personnel (2009), the Six Great Talent Peak Plan of Jiangsu (2010-WS-024), the National Science & Technology Pillar Program (2008BAI61B01), the Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU (2011), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (2011).

The authors thank Dr. Dexiu Bu (Brigham and Women's Hospital, Harvard Medical School, Boston, MA) for correcting the English grammar of this manuscript.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing, 210029, China

    Ping Liu, ZhongKun Lin, SiXuan Qian, Chun Qiao, HaiRong Qiu, YuJie Wu, JianYong Li & Zheng Ge

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  1. Ping Liu
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Correspondence to JianYong Li or Zheng Ge.

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Liu, P., Lin, Z., Qian, S. et al. Expression of dominant-negative Ikaros isoforms and associated genetic alterations in Chinese adult patients with leukemia. Ann Hematol 91, 1039–1049 (2012). https://doi.org/10.1007/s00277-012-1415-4

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