WT1 overexpression predicted good outcomes in adult B-cell acute lymphoblastic leukemia patients receiving chemotherapy

Hematology. 2020 Dec;25(1):118-124. doi: 10.1080/16078454.2020.1735670.

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.

Keywords: Acute lymphoblastic leukemia; Adult‌; BCR-ABL fusion; KMT2A rearrangements; WT1 expression; chemotherapy; hematopoietic stem cell transplantation; prognosis.

MeSH terms

  • Adolescent
  • Adult
  • Female
  • Humans
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Prognosis
  • Treatment Outcome
  • WT1 Proteins / metabolism*
  • Young Adult

Substances

  • WT1 Proteins
  • WT1 protein, human