Expression of WT1 gene in children with acute myeloid leukemia
TANG Xue, GUO Xia, YANG Xue, XIAO Hui, SUN Jing-Jing, YUAN Li-Xing, GAO Ju
Department of Pediatric Hematology & Oncology, West China Second University Hospital, Sichuan University;Key Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University), Ministry of Education, Chengdu 610041, China
Abstract Objective To study WT1 gene expression in children with acute myeloid leukemia (AML) and its possible correlations to clinical outcomes. Methods Bone marrow samples were collected from 45 children with AML (excluding acute promyelocytic leukemia, AML-M3) at different time points of AML treatment and follow-up. WT1 gene expression levels in bone marrow mononuclear cells were assayed by real-time fluorescence quantitative PCR. The correlation between WT1 expression and prognosis was retrospectively analyzed. Results The WT1 expression level in AML children with bone marrow blast cell percentage of > 60% was significantly higher than in those with bone marrow blast cell percentage of ≤ 60% (P < 0.05). The lower WT1 expression level was documented in children with AML-M2 compared with in children with other non-M2 subtypes (P < 0.05). WT1 expression level in patients in complete remission was significantly lower than that in patients at diagnosis or relapse (P < 0.01). The 2-year disease-free survival (DFS) in patients with higher WT1 expression was significantly lower than in those with lower WT1 expression at the end of induction chemotherapy (P < 0.05). The 2-year overall survival (OS) and DFS in patients with ≥1 log WT1 reduction range were significantly higher than those with < 1 log reduction of WT1 expression level at the end of induction chemotherapy (P < 0.05). WT1 expression levels tended to rise 2-3 months prior to bone marrow relapse. Conclusions WT1 expression level is closely correlated prognosis in children with AML. Dynamic monitoring of WT1 expression level is of great clinical importance in terms of individualized management, prognosis evaluation and relapse prediction.
Lee SB, Haber DA. Wilms tumor and the WT1 gene[J]. 2001, 264(1):74-99.
[2]
Qi XW, Zhang F, Wu H, et al. Wilms' tumor 1(WT1) expression and prognosis in solid cancer patients:a systematic review and meta-analysis[J]. Sci Rep, 2015, 5:8924.
[3]
Kramarzova K, Stuchly J, Willasch A, et al. Real-time PCR quantification of major Wilms tumor gene 1(WT1) isoforms in acute myeloid leukemia, their characteristic expression patterns and possible functional consequences[J]. Leukemia, 2012, 26(9):2086-2095.
[4]
Lyu X, Xin Y, Mi R, et al. Overexpression of Wilms tumor 1 gene as a negative prognosic indicator in acute myeloid leukemia[J]. PLoS One, 2014, 9(3):e92470.
[5]
Kitamura K, Nishiyama T, Ishiyama K, et al. Clinical usefulness of WT1 mRNA expression in bone marrow detected by a new WT1 mRNA assay kit for monitoring acute myeloid leukemia:a comparison with expression of WT1 mRNA in peripheral blood[J]. Int J Hematal, 2016, 103(1):53-62.
[6]
Miyawaki S, Hatsumi N, Tamaki T, et al. Prognostic potential of detection of WT1 mRNA level in peripheral blood in adult acute myeloid leukemia[J]. Leuk Lymphoma, 2010, 51(10):1855-1861.
[7]
Lasa A, Carricondo M, Estivill C, et al. WT1 monitoring in core binding factor AML:comparison with specific chimeric products[J]. Leuk Res, 2009, 33(12):1643-1649.
[8]
Pozzi S, Geroldi S, Tedone E, et al. Leukemia relapse after allogeneic transplants for acute myeloid leukemia:predictive role of WT1 expression[J]. Br J Haematol, 2013, 160(4):503-509.
[9]
Shibasaki Y, Seki Y, Tanaka T, et al. The association of level of reduction of Wilms' tumor gene 1 mRNA transcript in bone marrow and outcome in acute myeloid leukemia patients[J]. Leuk Res, 2015, 39(6):667-671.
[10]
Rossi G, Minervini MM, Melillo L, et al. Predictive role of minimal residual disease and log clearance in acute myeloid leukemia:a comparison between multiparameter flow cytometry and Wilm's tumor 1 levels[J]. Ann Hematol, 2014, 93(7):1149-1157.
[11]
Burnett AK, Hills RK, Milligan D, et al. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin:results of the MRC AML15 trial[J]. J Clin Oncol, 2011, 29(4):369-377.
[12]
Cheson BD, Cassileth PA, Head DR, et al. Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia[J]. J Clin Oncol,1990, 8(5):813-819.
Ommen HB, Nyvold CG, Braendstrup K, et al. Relapse prediction in acute myeloid leukemia patients in complete remission using WT1 as a molecular marker:development of a mathematical model to predict time from molecular to clinical relapse and define optimal sampling intervals[J]. Br J Haematol, 2008, 141(6):782-791.
[16]
Kim HJ, Choi EJ, Sohn HJ, et al. Combinatorial molecular marker assays of WT1, survivin, and TERT at initial diagnosis of adult acute myeloid leukemia[J]. Eur J Haematol, 2013, 91(5):411-422.
[17]
Luo S, Yu K, Yan QX, et al. Analysis of WT1 mutations, expression levels and single nucleotide polymorphism rs16754 in de novo non-M3 acute myeloid leukemia[J]. Leuk Lymphoma, 2014, 55(2):349-357.
[18]
Rodrigues PC, Oliveira SN, Viana MB, et al. Prognostic significance of WT1 gene expression in pediatric acute myeloid leukemia[J]. Pediatr Blood Cancer, 2007, 49(2):133-138.
[19]
Noronha SA, Farrar JE, Alonzo TA, et al. WT1 expression at diagnosis does not predict survival in pediatric AML:a report from the Children's Oncology Group[J]. Pediatr Blood Cancer, 2009, 53(6):1136-1139.
[20]
Nomdedéu JF, Hoyos M, Carricondo M, et al. Bone marrow WT1 levels at diagnosis, post-induction and post-intensification in adult de novo AML[J]. Leukemia, 2013, 27(11):2157-2164.
