Incidence and Prognostic Impact of WT-1 Gene Exon7 and 9 Mutations in Acute Promyelocytic Leukemia

Fatemeh Nejatifar; Shahrbano Rostami; Barham chahardouli; Amir Kasaeian; Mohammad Vaezi; Hossein Kamranzadeh; Seied Asadollah Mousavi; Abolfazl Farbod; Kamran Alimoghaddam; Ardeshir Ghavamzadeh

doi:10.18502/ijhoscr.v16i2.9199

Fatemeh Nejatifar Department of Hematology and Oncology, Guilan University of Medical Sciences, Rasht, Iran
Shahrbano Rostami Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran
Barham chahardouli Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran
Amir Kasaeian Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran
Mohammad Vaezi Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran
Hossein Kamranzadeh Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran
Seied Asadollah Mousavi Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran
Abolfazl Farbod Department of Dermatology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Kamran Alimoghaddam Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran
Ardeshir Ghavamzadeh Cancer & Cell Therapy Research Center, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijhoscr.v16i2.9199

Keywords: WT1 mutation; Acute promyelocytic leukemia; Prognosis

Abstract

Background: Wilms’ tumor gene 1 (WT1) gene mutation has been reported to be a prognostic factor in normal-cytogenetic acute myeloid leukemia (AML) patients. Higher rates of mutation in the WT1 gene have been reported in several tumors including normal-cytogenetic AML patients. Data regarding WT1 mutations in acute promyelocytic leukemia (APL) is very scarce. In this study, we evaluated the incidence and impact of WT1 mutation on the outcome of APL patients.

Materials and Methods: A total of 92 patients diagnosed with APL were studied in three distinct groups: early mortality, relapsed, and persistent complete remission. Genomic DNA of bone marrow samples of patients was analyzed. For quantification of expression levels of the WT1 gene, real-time quantitative PCR (rqPCR) was performed by a real-time PCR system. WT1 mutation and its impact on prognosis were considered the primary endpoint of the study. Statistical analysis was performed with STATA.

Results: WT1 mutation frequency was 6.25% in the early mortality group (1/16 patients), 13.16% in the relapse group (5/38 patients), and 7.89% in the persistent complete remission group (3/38 patients). 8 mutations were in exon 7 and one mutation in exon 9. WT1 mutation in the relapse group was associated with a trend toward worse disease-free survival (DFS) while overall survival (OS) was not affected by WT1 mutation in univariate analysis. Patients with no mutations in WT1 and FLT3/ITD had better overall survival and disease-free survival compared to patients with mutations in the WT1 gene or FLT3/ITD in the relapse group.

Conclusion: The frequency of WT1 gene mutations does not differ significantly between patients with early mortality, relapse, and persistent complete remission. The presence of WT1 mutation is associated with higher relapse and lower survival rates in relapse group patients.