Abstract
ABSTRACT Objectives: The prognostic role of WT1 in acute lymphoblastic leukemia (ALL) is still controversial. No study has focused on the prognostic role of WT1 expression in adult B-ALL patients receiving chemotherapy only. Methods: Using TaqMan-based real time quantitative PCR (RQ-PCR), we detected the WT1 transcript levels of 162 de-novo adult B-ALL patients at the time of diagnosis and analysed their clinical features. Results: WT1 overexpression was defined as a transcript level higher than 0.50%, which is the upper limit in normal bone marrow. WT1 overexpression was identified in 66.0% of the patients and was an independent positive prognostic factor for CIR, RFS and OS in patients who received chemotherapy only (CIR: HR = 0.236 [95% confidence interval 0.094–0.592]; P = 0.002; RFS: HR = 0.223 [0.092–0.543]; P = 0.001; OS: HR = 0.409 [0.214–0.783]; P = 0.007) and in patients who did not have BCR-ABL fusion or KMT2A rearrangements (CIR: HR = 0.431 [0.201–0.921]; P = 0.030; RFS: HR = 0.449 [0.224–0.899]; P = 0.024; OS: HR = 0.521 [0.278–0.977]; P = 0.042). However, WT1 overexpression had no prognostic value in patients who received allogenic hematopoietic stem cell transplantation (allo-HSCT). Furthermore, allo-HSCT could improve the prognosis of patients with low WT1 expression. Conclusion: Therefore, testing for WT1 expression at the time of diagnosis may predict outcomes in adult B-ALL patients who receive only chemotherapy and who do not have the BCR-ABL fusion gene or KMT2A rearrangements. Allo-HSCT may improve the prognosis of patients with low WT1 transcript levels.
Highlights
B-cell acute lymphoblastic leukemia (B-ALL) is a clinically and biologically heterogeneous disease that is characterized by the clonal expansion of developmentally arrested B-cell precursors [1]
Wilms’ tumor gene 1 (WT1) overexpression was identified in 66.0% of the patients and was an independent positive prognostic factor for cumulative incidence of relapse (CIR), Relapse-free survival (RFS) and OS in patients who received chemotherapy only (CIR: HR = 0.236 [95% confidence interval 0.094–0.592]; P = 0.002; RFS: HR = 0.223 [0.092–0.543]; P = 0.001; OS: HR = 0.409 [0.214–0.783]; P = 0.007) and in patients who did not have BCR-ABL fusion or KMT2A rearrangements (CIR: HR = 0.431 [0.201– 0.921]; P = 0.030; RFS: HR = 0.449 [0.224–0.899]; P = 0.024; OS: HR = 0.521 [0.278–0.977]; P = 0.042)
The results showed that WT1 overexpression, female sex and no KMT2A rearrangements were associated with lower CIR; WT1 overexpression, female sex, no KMT2A rearrangements and measurable residual disease (MRD)
Summary
B-cell acute lymphoblastic leukemia (B-ALL) is a clinically and biologically heterogeneous disease that is characterized by the clonal expansion of developmentally arrested B-cell precursors [1]. Adults with B-ALL who have none of the adverse prognostic variables remain clinically heterogeneous with varied outcomes. Whether WT1 transcript levels at the time of diagnosis can predict outcomes in AML patients is still controversial [6,7,8,9,10,11]. The prognostic role of WT1 in ALL is even less clear and more controversial than its role in AML [12,13,14,15,16,17,18,19,20,21] This indicates that the mechanism of action of WT1 is complex and that WT1 may play the role of an oncogene or a tumor suppressor gene in different tumors or different subgroups of tumors. No study has focused on the prognostic role of WT1 expression in different subgroups of adult B-ALL patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
