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Prognostic significance of P2RY8-CRLF2 and CRLF2 overexpression may vary across risk subgroups of childhood B-cell acute lymphoblastic leukemia.
Genes Chromosomes Cancer 2017; 56(2):135-146GC

Abstract

The cytokine receptor-like factor 2 (CRLF2) gene plays an important role in early B-cell development. Aberrations in CRLF2 activate the JAK-STAT signaling pathway that contributes to B-cell acute lymphoblastic leukemia (B-ALL). The prognostic significance of CRLF2 overexpression and P2RY8-CRLF2 fusion in various B-ALL risk subgroups has not been well established. Two hundred seventy-one patients with newly diagnosed childhood B-ALL were enrolled from a Chinese population. The prevalence of CRLF2 overexpression, CRLF2-P2RY8 fusion, CRLF2 F232C mutation, and JAK2 and IL7R mutational status were analyzed, and the prognostic impact of CRLF2 overexpression and P2RY8-CRLF2 on B-ALL was evaluated by assessing their influence on overall survival and event-free survival. CRLF2 overexpression and P2RY8-CRLF2 were found in 19% and 10%, respectively, in the whole cohort. No correlation between CRLF2 overexpression and P2RY8-CRLF2 was observed. CRLF2 F322C and IL7R mutations were not detected in B-ALL cases overexpressing CRLF2, and no JAK2 mutations were found in the whole cohort either. The results showed that CRLF2 overexpression and P2RY8-CRLF2 were associated with a poor outcome in unselected B-ALL. Moreover, in an intermediate risk B-ALL subgroup P2RY8-CRLF2 was correlated with worse survival, whereas in high- and low-risk subgroups, CRLF2 overexpression predicted a poor outcome. Our findings suggest that P2RY8-CRLF2 is an independent prognostic indicator in intermediate risk B-ALL, while CRLF2 overexpression is correlated with an inferior outcome in high- or low-risk B-ALL. Our study demonstrates that the impact of P2RY8-CRLF2 and CRLF2 overexpression on B-ALL survival may differ across risk subgroups. © 2016 Wiley Periodicals, Inc.

Authors+Show Affiliations

Department of Clinical Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.Center for Clinical Molecular Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China.Research Center for Immunity and Infectious Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China.Department of Hematology and Oncology, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China.Department of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China.Department of Hematology and Oncology, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China.Department of Clinical Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. Ministry of Education Key Laboratory of Clinical Laboratory Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.Center for Clinical Molecular Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China. Department of Pathology and Laboratory Medicine, Geisel School of Medicine Dartmouth College, New Hampshire, USA.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27637012

Citation

Dou, Hu, et al. "Prognostic Significance of P2RY8-CRLF2 and CRLF2 Overexpression May Vary Across Risk Subgroups of Childhood B-cell Acute Lymphoblastic Leukemia." Genes, Chromosomes & Cancer, vol. 56, no. 2, 2017, pp. 135-146.
Dou H, Chen X, Huang Y, et al. Prognostic significance of P2RY8-CRLF2 and CRLF2 overexpression may vary across risk subgroups of childhood B-cell acute lymphoblastic leukemia. Genes Chromosomes Cancer. 2017;56(2):135-146.
Dou, H., Chen, X., Huang, Y., Su, Y., Lu, L., Yu, J., ... Bao, L. (2017). Prognostic significance of P2RY8-CRLF2 and CRLF2 overexpression may vary across risk subgroups of childhood B-cell acute lymphoblastic leukemia. Genes, Chromosomes & Cancer, 56(2), pp. 135-146. doi:10.1002/gcc.22421.
Dou H, et al. Prognostic Significance of P2RY8-CRLF2 and CRLF2 Overexpression May Vary Across Risk Subgroups of Childhood B-cell Acute Lymphoblastic Leukemia. Genes Chromosomes Cancer. 2017;56(2):135-146. PubMed PMID: 27637012.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prognostic significance of P2RY8-CRLF2 and CRLF2 overexpression may vary across risk subgroups of childhood B-cell acute lymphoblastic leukemia. AU - Dou,Hu, AU - Chen,Xi, AU - Huang,Yi, AU - Su,Yongchun, AU - Lu,Ling, AU - Yu,Jie, AU - Yin,Yibing, AU - Bao,Liming, Y1 - 2016/11/05/ PY - 2016/05/21/received PY - 2016/09/06/revised PY - 2016/09/07/accepted PY - 2016/9/17/pubmed PY - 2017/7/22/medline PY - 2016/9/17/entrez SP - 135 EP - 146 JF - Genes, chromosomes & cancer JO - Genes Chromosomes Cancer VL - 56 IS - 2 N2 - The cytokine receptor-like factor 2 (CRLF2) gene plays an important role in early B-cell development. Aberrations in CRLF2 activate the JAK-STAT signaling pathway that contributes to B-cell acute lymphoblastic leukemia (B-ALL). The prognostic significance of CRLF2 overexpression and P2RY8-CRLF2 fusion in various B-ALL risk subgroups has not been well established. Two hundred seventy-one patients with newly diagnosed childhood B-ALL were enrolled from a Chinese population. The prevalence of CRLF2 overexpression, CRLF2-P2RY8 fusion, CRLF2 F232C mutation, and JAK2 and IL7R mutational status were analyzed, and the prognostic impact of CRLF2 overexpression and P2RY8-CRLF2 on B-ALL was evaluated by assessing their influence on overall survival and event-free survival. CRLF2 overexpression and P2RY8-CRLF2 were found in 19% and 10%, respectively, in the whole cohort. No correlation between CRLF2 overexpression and P2RY8-CRLF2 was observed. CRLF2 F322C and IL7R mutations were not detected in B-ALL cases overexpressing CRLF2, and no JAK2 mutations were found in the whole cohort either. The results showed that CRLF2 overexpression and P2RY8-CRLF2 were associated with a poor outcome in unselected B-ALL. Moreover, in an intermediate risk B-ALL subgroup P2RY8-CRLF2 was correlated with worse survival, whereas in high- and low-risk subgroups, CRLF2 overexpression predicted a poor outcome. Our findings suggest that P2RY8-CRLF2 is an independent prognostic indicator in intermediate risk B-ALL, while CRLF2 overexpression is correlated with an inferior outcome in high- or low-risk B-ALL. Our study demonstrates that the impact of P2RY8-CRLF2 and CRLF2 overexpression on B-ALL survival may differ across risk subgroups. © 2016 Wiley Periodicals, Inc. SN - 1098-2264 UR - https://www.unboundmedicine.com/medline/citation/27637012/Prognostic_significance_of_P2RY8_CRLF2_and_CRLF2_overexpression_may_vary_across_risk_subgroups_of_childhood_B_cell_acute_lymphoblastic_leukemia_ L2 - https://doi.org/10.1002/gcc.22421 DB - PRIME DP - Unbound Medicine ER -