J Cancer 2019; 10(16):3842-3850. doi:10.7150/jca.33989 This issue Cite

Research Paper

RAG1 high expression associated with IKZF1 dysfunction in adult B-cell acute lymphoblastic leukemia

Qi Han1,2, Jinlong Ma1,2, Yan Gu1,2, Huihui Song1,2, Malika Kapadia3, Yuka Imamura Kawasawa2,4, Sinisa Dovat2,3, Chunhua Song2,3, Zheng Ge1,2,✉

1. Department of Hematology, Zhongda Hospital, Medical School of Southeast University, Institute of Hematology Southeast University,Nanjing 210009, China
2. International Cooperative Leukemia Group and International Cooperative Laboratory of Hematology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China
3. Department of Pediatrics, Pennsylvania State University Medical College, Hershey, PA17033, USA
4. Genome Sciences and Bioinformatics Core Facility, Institute for Personalized Medicine, Penn State College of Medicine, Hershey, PA17033, USA

Citation:
Han Q, Ma J, Gu Y, Song H, Kapadia M, Kawasawa YI, Dovat S, Song C, Ge Z. RAG1 high expression associated with IKZF1 dysfunction in adult B-cell acute lymphoblastic leukemia. J Cancer 2019; 10(16):3842-3850. doi:10.7150/jca.33989. https://www.jcancer.org/v10p3842.htm
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Abstract

The recombination mediated by recombination activating gene (RAG) is not only the dominant mutational process but also the predominant driver of oncogenic genomic rearrangement in acute lymphoblastic leukemia (ALL). It is further responsible for leukemic clonal evolution. In this study, significant RAG1 increase is observed in the subsets of B-ALL patients, and high expression of RAG1 is observed to be correlated with high proliferation markers. IKZF1-encoded protein, IKAROS, directly binds to the RAG1 promoter and regulates RAG1 expression in leukemic cells. CK2 inhibitor by increasing IKAROS activity significantly suppresses RAG1 expression in ALL in an IKAROS-dependent manner. Patients with IKZF1 deletion have significantly higher expression of RAG1 compared to that without IKZF1 deletion. CK2 inhibitor treatment also results in an increase in IKZF1 binding to the RAG1 promoter and suppression of RAG1 expression in primary ALL cells. Taken together, these results demonstrate that RAG1 high expression is associated with high proliferation markers in B-ALL. Our data for the first time proved that RAG1 expression is directly suppressed by IKAROS. Our results also reveal drive oncogenesis of B-ALL is driven by high expression of RAG1 with IKAROS dysfunction together, which have significance in an integrated prognostic model for adult ALL.

Keywords: RAG1, IKZF1, adult, acute lymphoblastic leukemia


Citation styles

APA
Han, Q., Ma, J., Gu, Y., Song, H., Kapadia, M., Kawasawa, Y.I., Dovat, S., Song, C., Ge, Z. (2019). RAG1 high expression associated with IKZF1 dysfunction in adult B-cell acute lymphoblastic leukemia. Journal of Cancer, 10(16), 3842-3850. https://doi.org/10.7150/jca.33989.

ACS
Han, Q.; Ma, J.; Gu, Y.; Song, H.; Kapadia, M.; Kawasawa, Y.I.; Dovat, S.; Song, C.; Ge, Z. RAG1 high expression associated with IKZF1 dysfunction in adult B-cell acute lymphoblastic leukemia. J. Cancer 2019, 10 (16), 3842-3850. DOI: 10.7150/jca.33989.

NLM
Han Q, Ma J, Gu Y, Song H, Kapadia M, Kawasawa YI, Dovat S, Song C, Ge Z. RAG1 high expression associated with IKZF1 dysfunction in adult B-cell acute lymphoblastic leukemia. J Cancer 2019; 10(16):3842-3850. doi:10.7150/jca.33989. https://www.jcancer.org/v10p3842.htm

CSE
Han Q, Ma J, Gu Y, Song H, Kapadia M, Kawasawa YI, Dovat S, Song C, Ge Z. 2019. RAG1 high expression associated with IKZF1 dysfunction in adult B-cell acute lymphoblastic leukemia. J Cancer. 10(16):3842-3850.

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