The Levels of FoxO3a Predict the Failure of Imatinib Mesylate Therapy among Chronic Myeloid Leukemia Patients

Abstract

INTRODUCTION: Forkhead Transcription Factor 3a (FoxO3a) has been proposed to have a high efficacy to predict the failure of imatinib mesylate (IM) therapy among Chronic Myeloid Leukemia (CML) patients. However, the limited evidence had made this marker remained controversy.
 OBJECTIVES: We aimed to investigate the correlation between the levels of FoxO3a and the risk of treatment failure of IM therapy in CML patients.
 METHODS: A prospective cohort study was carried out between February 2019 and February 2020 in Saiful Anwar Hospital, Malang, Indonesia. All CML patients treated with IM on our hospital during the study period were included. The levels of FoxO3a was determined using the Enzyme-linked immunosorbent assay (ELISA) using Cusabio Biotech Kit (Cusabio Biotech Co., New York, USA). The treatment response was assessed using the European Leukemia criteria. The correlation and effect estimate between the levels of FoxO3a and treatment response of CML patients was assessed using multiple logistic regression.
 RESULTS: 53 CML patients receiving IM in our hospital were included, consisting of 29 patients with good response and 24 patients with non-response. Our study found that CML patients with lower levels of FoxO3a was associated with increased risk to develop treatment failure when treated with IM. Moreover, we also found that higher risk of treatment failure of IM therapy was also found in patients with increased levels of thrombocytes, basophils, and leukocytes, and lower levels of hemoglobin.
 CONCLUSION: We reveal that FoxO3a is the prominent marker to predict the treatment response of CML patients treated with IM.

The association between FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a among chronic granulocytic leukemia patients treated with imatinib mesylate

“…They found that elevated levels of FOXO3a was associated with treatment failure of CGL patient treated with imatinib mesylate, suggesting that the levels of FOXO3a might play an important role to contribute the progression of CGL. 16 Furthermore, studies also found that elevated levels of FOXO3a was associated with adverse prognosis of leukemia. 24,25 However, geneenvironment interaction should also be considered to affect the disease progression since it was proven that the FOXO transcription factors had various impact in different population, for example: the role of FOXO transcription factors were found inconclusive to affect the human longevity in the population of Japan, Germany, Italia, and Indonesia.…”

“…Patients were excluded from our study if they had a history of the following conditions: prostate cancer, gynecological cancer, COPD, breast cancer, vitiligo, and thyroid cancer. 16 Our present study was conducted following the ethics code of the Helsinki Declaration and was registered and approved by the Ethical Committee of Universitas Brawijaya (No. 400/098/k.3/302/2019).…”

The association between FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a among chronic granulocytic leukemia patients treated with imatinib mesylate

“…They found that elevated levels of FOXO3a was associated with treatment failure of CGL patient treated with imatinib mesylate, suggesting that the levels of FOXO3a might play an important role to contribute the progression of CGL. 16 Furthermore, studies also found that elevated levels of FOXO3a was associated with adverse prognosis of leukemia. 24 , 25 However, gene – environment interaction should also be considered to affect the disease progression since it was proven that the FOXO transcription factors had various impact in different population, for example: the role of FOXO transcription factors were found inconclusive to affect the human longevity in the population of Japan, Germany, Italia, and Indonesia.…”

The association between FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a among chronic granulocytic leukemia patients treated with imatinib mesylate

“…Patients were excluded from our study if they had a history of the following conditions: prostate cancer, gynecological cancer, COPD, breast cancer, vitiligo, and thyroid cancer. 15 Our present study was conducted following the ethics code of the Helsinki Declaration and was registered and approved by the Ethical Committee of Universitas Brawijaya (No. 400/098/k.3/302/2019).…”