WT1 Correlates With Survival in Intermediate-, Poor-Risk Acute Myeloid Leukemia

Expression of the Wilms’ tumor 1 (WT1) gene appears to be predictive for survival outcomes in patients with intermediate- and high-risk acute myeloid leukemia (AML), according to the results of a study published in Clinical Lymphoma, Myeloma and Leukemia.

WT1, which encodes a transcriptional regulator for genes involved in cell growth and maturation, is known to be overexpressed in bone marrow and peripheral blood in several leukemias, including AML (about 90% of AML).

A team of investigators in Czech Republic aimed to evaluate the prognostic value of WT1 gene expression during the early stages of intensive chemotherapy in patients with intermediate- and high-risk AML, groups that often lack specific genetic lesions or clonality markers to assess molecular response.

WT1 gene expression was retrospectively analyzed in peripheral blood from 272 patients who were diagnosed and treated at the Institute of Haematology and Blood Transfusion in Prague, Czech Republic, from 2009 to 2015.

Adult patients were categorized into 3 groups based on WT1 level: low expressors (0-499 WT1 copies/10⁴ copies of the reference gene Abelson [ABL]; 27 patients), intermediate expressors (500-4999 WT1 copies/10⁴ ABL; 82 patients) and high expressors (≥5000 WT1 copies/10⁴ ABL; 163 patients).

The dynamics of WT1 expression were assessed in a subset of 106 patients (range, 21-66 years) with intermediate- or poor-risk cytogenetics and who had WT1 expression of >500 copies/10⁴ ABL at diagnosis and achieved remission after 1 to 2 cycles of induction treatment. Overexpression of WT1 was defined as >50 copies/10⁴ ABL. The median follow-up duration was 30 months (range, 5-106 months).

After 2 cycles of chemotherapy, overexpression of WT1 was associated with lower 3-year overall survival (OS) and event-free survival. The OS for normal vs high WT1 expression was 66% vs 41%, respectively (P =.01); the EFS for normal vs high WT1 expression was 45% vs 22%, respectively(P =.01).

The prognostic value of WT1 expression persisted when comparing patients treated with chemotherapy alone (without hematopoietic stem cell transplantation in first-line treatment) with normal vs high WT1 expression (OS, 70% vs 36%, respectively; P =.02; EFS, 35% vs 0%, respectively; P =.03).

In a multivariate analysis, the achievement of molecular remission (<50 copies of WT1) at any time during treatment (hazard ratio [HR], 0.47; P =.04) and increased WT1 expression after 2 cycles of chemotherapy (HR, 2.0; P =.03) were significantly associated with EFS.

Limitations of the study included its retrospective nature and single-center design.

“Increased WT1 expression after 2 cycles of chemotherapy is a negative prognostic factor for survival. WT1 remains a valuable molecular marker in AML without any [leukemia]-specific mutation, especially if next generation sequencing and/or digital [polymerase chain reaction] are not routinely available,” wrote the authors. “Patients with high WT1 expression after 2 cycles of intensive treatment could benefit from intensification of further therapy.”

Reference

Šálek C, Vydra J, Cerovská E, et al. WT1 expression in peripheral blood at diagnosis and during the course of early consolidation treatment correlates with survival in patients with intermediate and poor risk acute myeloid leukaemia. Clin Lymphoma Myeloma Leuk. Published online August 10, 2020. doi:10.1016/j.clml.2020.07.014