Abstract

Purpose: Acute myeloid leukemia (AML) is the most prevalent acute leukemia in adults. It possesses different cytogenetic and molecular features. The expression of Wilms tumor-1 (WT1), brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) might be considered as prognostic factors in AML patients. The aim of this study was to determine the mRNA expressions of WT-1, BAALC and ERG genes in bone marrow of mononuclear cells and their effects on complete remission in the Iranian AML patients, pre- and post- chemotherapy. Methods: Forty AML patients with normal karyotype were evaluated. The mRNA gene expressions were measured with quantitative real-time PCR in bone marrow of mononuclear cells of AML patients at the baseline and after chemotherapy. The subtypes of AML and flow cytometry panel were also assessed. Complete remission (CR) after the treatment was addressed for all patients. Results: The mRNA expressions of WT-1, BAALC and ERG were significantly decreased after the treatment (p = 0.001, 0.017, 0.036). WT-1 mRNA expression was inversely correlated with CR after chemotherapy (P =0.024). There was also significant correlation between baseline expression of BAALC and CR (P =0.046). No significant correlation was observed between ERG and CR pre- and post- chemotherapy (P =0.464 and 0.781). There was also significant correlation between BAALC mRNA expression and CD34+ (P <0.001). Conclusion: The present study showed that WT-1 decreased significantly after standard chemotherapy which could have favorable effects on CR. Also, the high expression of BAALC could have a poor prognostic role in AML patients. The identification of these gene expressions can be an efficient approach in targeted therapy among AML patients.

Highlights

  • Acute myeloid leukemia (AML) is the most prevalent acute leukemia in adults encompassing 80% of cases of this group.[1]

  • The aim of this study was to determine the mRNA expressions of Wilms tumor 1 (WT-1), BAALC and ETS-related gene (ERG) genes in bone marrow of mononuclear cells and their effects on complete remission in the Iranian AML patients, pre- and post- chemotherapy

  • Previous studies reported that the ratio of WT-1 in pre- and post- chemotherapy phases was considered as a predictor of disease outcome in AML patients who have undergone “3+7” chemotherapy.[20]

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Summary

Introduction

Acute myeloid leukemia (AML) is the most prevalent acute leukemia in adults encompassing 80% of cases of this group.[1] It is a malignancy characterized by the abnormal differentiation and proliferation of myeloid stem cells clonal population.[2] Some special chromosomal alterations can lead to the formation of chimeric proteins which in turn may increase the likelihood of malignant transformation.[3]. The Wilms tumor 1 (WT-1) locus in chromosomal region 11p13; encodes a transcription factor highly expressed in the cells of the majority of leukemia patients at diagnosis, and apparently participates in leukemogenesis.[5] High expression of WT-1 in acute leukemia has been reported to represent a molecular marker of malignant hematopoiesis and was associated with fewer remissions and poor overall survival.[6,7]

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