WT-1, BAALC, and ERG Expressions in Iranian Patients with Acute Myeloid Leukemia Pre- and Post-chemotherapy

• Published in: Advanced pharmaceutical bulletin 2021-01, Vol.11 (1), p.197-203
• Main Authors: Mehralizadeh, Hossein, Aliparasti, Mohammad Reza, Talebi, Mehdi, Salekzamani, Shabnam, Almasi, Shohreh, Raeisi, Morteza, Yousefi, Mehdi, Movassaghpour, AliAkbar
• Format: Article
• Language: English
• Subjects: acute myeloid leukemia; baalc; Bone marrow; Chemotherapy; erg; Flow cytometry; Gene expression; Leukemia; Medical prognosis; Transcription factors; wt-1
• ISSN: 2228-5881; 2251-7308
• DOI: 10.34172/apb.2021.021

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 AML is a heterogeneous disease with possessing different cytogenetic and molecular features which are considered as the key prognostic factors predicting the risk of survival and relapse.3 Recent advances in treatment protocols are based on these prognostic factors contributing to individualized therapy and risk-adapted intensification.4 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 Another molecular change in AML is the deregulated expression of brain and acute leukemia-cytoplasmic (BAALC) gene. BAALC, which maps on chromosome 8 at 8q22.3, is involved in neuroectodermal and hematopoietic development.8 The expression of BAALC was reported as a precursor for hematopoiesis like the cluster of differentiation CD34+ in early hematopoietic cells.9 High expression of that was found in bone marrow of AML patients with a normal karyotype10 and identified as an independent poor prognostic indicator, associated with shorter survival.11 No specific role was explained for BAALC in leukemogenesis, but it was suggested that it blocks myeloid differentiation.12 It was suggested that high expression of BAALC is associated with a poor outcome in AML patients.13 Moreover, ETS-related gene (ERG) located on chromosome band 21q22, is a transcription factor required for normal hematopoiesis.14 The elevated expression of ERG was demonstrated in cytogenetically normal AML patients and has a negative role in the prognosis of AML.15,16 The role of standard treatment in the expression of these genes as well as the effect of posttreatment molecular changes on complete remission (CR) are not clearly investigated in the Iranian population. The up-regulation of BAALC was reported with survivability reduction.17 In another stu