Significance of PAX5 deletion in childhood B-lineage acute lymphoblastic leukemia without reproducible chromosomal abnormalities

LIU Xiao-Ming; ZHANG Li; RUAN Min; LIU Tian-Feng; ZHANG Jia-Yuan; LIU Fang; QI Ben-Quan; CHEN Xiao-Juan; WANG Shu-Chun; YANG Wen-Yu; GUO Ye; ZOU Yao; CHEN Yu-Mei; ZHU Xiao-Fan

doi:10.7499/j.issn.1008-8830.2016.04.001

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Chinese Journal of Contemporary Pediatrics ›› 2016, Vol. 18 ›› Issue (4) : 287-291. DOI: 10.7499/j.issn.1008-8830.2016.04.001

CLINICAL RESEARCH

Significance of PAX5 deletion in childhood B-lineage acute lymphoblastic leukemia without reproducible chromosomal abnormalities

LIU Xiao-Ming, ZHANG Li, RUAN Min, LIU Tian-Feng, ZHANG Jia-Yuan, LIU Fang, QI Ben-Quan, CHEN Xiao-Juan, WANG Shu-Chun, YANG Wen-Yu, GUO Ye, ZOU Yao, CHEN Yu-Mei, ZHU Xiao-Fan

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Abstract

Objective To identify the incidence of PAX5 deletion in childhood B-lineage acute lymphoblastic leukemia (B-ALL) without reproducible chromosomal abnormalities and to investigate the association between PAX5 abnormalities and prognosis of ALL. Methods Multiplex ligation-dependent probe amplification was used to determine the copy numbers of PAX5 gene in children newly diagnosed with B-ALL without reproducible chromosomal abnormalities between April 2008 and April 2013 and controls (children with non-hematologic diseases or tumors). The patients were classifiied into deletion group and non-deletion group based on the presence of PAX5 deletion. Results Eighteen (21%) out of 86 children with B-ALL had PAX5 deletion. The deletion group had a significantly higher total white blood cell count at diagnosis than the non-deletion group (P=0.001). The Kaplan-Meier analysis demonstrated that the deletion group had a significantly lower disease-free survival (DFS) rate than the non-deletion group (0.69±0.12 vs 0.90±0.04; P=0.017), but there was no significant difference in the overall survival rate between the two groups (P=0.128). The Cox analysis showed that PAX5 deletion was a risk factor for DFS (P=0.03). Conclusions PAX5 deletion is an independent risk factor for DFS in B-ALL children without reproducible chromosomal abnormalities.

Key words

PAX5 / B-lineage acute lymphoblastic leukemia / Multiplex ligation-dependent probe amplification / Prognosis / Child

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LIU Xiao-Ming, ZHANG Li, RUAN Min, LIU Tian-Feng, ZHANG Jia-Yuan, LIU Fang, QI Ben-Quan, CHEN Xiao-Juan, WANG Shu-Chun, YANG Wen-Yu, GUO Ye, ZOU Yao, CHEN Yu-Mei, ZHU Xiao-Fan. Significance of PAX5 deletion in childhood B-lineage acute lymphoblastic leukemia without reproducible chromosomal abnormalities[J]. Chinese Journal of Contemporary Pediatrics. 2016, 18(4): 287-291 https://doi.org/10.7499/j.issn.1008-8830.2016.04.001

References

[1] Pui CH, Pei D, Campana D, et al. A revised definition for cure of childhood acute lymphoblastic leukemia[J]. Leukemia, 2014, 28(12): 2336-2343.
[2] Conter V, Bartram CR, Valsecchi MG, et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study[J]. Blood, 2010, 115(16): 3206-3214.
[3] Mullighan CG, Goorha S, Radtke I, et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia[J]. Nature, 2007, 446(7137): 758-764.
[4] Zhang J, Mullighan CG, Harvey RC, et al. Key pathways are frequently mutated in high-risk childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group[J]. Blood, 2011(11), 118: 3080-3087.
[5] Shahjahani M, Norozi F, Ahmadzadeh A, et al. The role of Pax5 in leukemia: diagnosis and prognosis significance[J]. Med Oncol, 2015, 32(1):360.
[6] Cozma D, Yu D, Hodawadekar S, et a1. B cell activator PAX5 promotes lymphomagenesis through stimulation of B cell receptor signaling[J]. J Clin Invest, 2007, 117(9): 2602-2610.
[7] 郑积富, 董莎莎, 王谦, 等. 伴有9p 异常的急性B 淋巴细胞白血病患者PAX5基因重排及缺失的研究[J]. 中华医学遗传学杂志, 2013, 30(5): 549-552.
[8] Teo AE, Chen Z, Miranda RN, et al. Differential PAX5 levels promote malignant B-cell infiltration, progression and drug resistance, and predict a poor prognosis in MCL patients independent of CCND1[J]. Leukemia, 2016, 30(3): 580-593.
[9] 秘营昌, 卞寿庚. 急性淋巴细胞白血病[M]//张之南, 沈悌. 血液病诊断及疗效标准. 第3 版. 北京: 科学出版社, 2007: 116-121.
[10] Gao C, Zhao XX, Li WJ, et a1. Clinical features, early treatment responses, and outcomes of pediatric acute lymphoblastic leukemia in China with or without specific fusion transcripts: a single institutional study of 1,004 patients[J]. Am J Hematol, 2012, 87(11):1022-1027.
[11] 刘晓明, 邹尧, 王慧君, 等. CCLG^-2008 方案治疗标危中危儿童急性淋巴细胞白血病中期随访结果[J]. 中华儿科杂志, 2014, 52(6): 449-454.
[12] 秘营昌, 卞寿庚. 急性白血病[M]//张之南, 沈悌. 血液病诊断及疗效标准. 第3 版. 北京: 科学出版社, 2007: 131-134.
[13] Dörge P, Meissner B, Zimmermann M, et al. IKZF1 deletion is an independent predictor of outcome in pediatric acute lymphoblastic leukemia treated according to the ALL-BFM 2000 protocol[J]. Haematologica. 2013, 98(3): 428-432.
[14] Ribera J, Morgades M, Zamora L, et al. Prognostic significance of copy number alterations in adolescent and adult patients with precursor B acute lymphoblastic leukemia enrolled in PETHEMA protocols[J]. Cancer. 2015, 121(21): 3809-3817.
[15] Stasevich I, Inglott S, Austin N, et al. PAX5 alterations in genetically unclassified childhood Precursor B-cell acute lymphoblastic leukaemia[J]. Br J Haematol, 2015, 171(2): 263-272.