HIF2-α Expression in CML Patients Receiving Hydroxyurea Prior to Imatinib That Achieved Major Molecular Response (MMR) versus in Those Not Achieving MMR

Abstract

Ikhwan Rinaldi,1,2 Radinal Mauludi,2 Sri Widia Jusman,3 Robert Sinto,4 Kuntjoro Harimurti5,6 1Division of Hematology and Medical Oncology, Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 2Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 3Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 4Division of Tropical and Infectious Diseases, Department of Internal Medicine, Cipto Mangunkusumo National General hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 5Clinical Epidemiology Unit, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia; 6Division of Geriatrics, Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaCorrespondence: Ikhwan Rinaldi, Email [email protected]: Currently, Imatinib (IM) which is a Tyrosine Kinase Inhibitor (TKI), is the main treatment for patients with chronic myeloid leukemia (CML). Major molecular response (MMR) is used as therapeutic response. Resistance to IM may be caused by hypoxia which is regulated by hypoxia inducible factor (HIF) 2-α. The role of HIF2-α is currently not researched extensively. This study aimed to analyse the differences in HIF-2α expression between chronic phase CML patients that achieved MMR and those that did not achieve MMR.Methods: This study used a cross-sectional method which analysed secondary data from whole blood samples in chronic phase CML patients aged 18– 60 years that received hydroxyurea (HU) before IM, aged 18– 60 years, received IM therapy for more than 12 months, and were willing to participate in the study. The exclusion criteria for this study were patients who were receiving IM at a dose of more than 400 mg/day. HIF-2α protein expression was examined using the enzyme-linked immunosorbent assay (ELISA) method. Differences between HIF-2α protein expression in groups that achieved MMR versus not achieving MMR was analysed using the Mann–Whitney test.Results: A total of 79 subjects were obtained. The median HIF-2α was 90.56 pg/mg protein (3.01– 4628.74). There was no statistically significant difference in expression of HIF-2α in the group that reached MMR and did not reach MMR, namely 123.45 pg/mg protein and 89.25 pg/mg protein respectively (p 0.718).Conclusion: This study found no statistically significant difference between HIF-2α expression level and MMR achievement of chronic phase CML patients who received HU before IM therapy.Keywords: CML, leukemia, imatinib, resistance, chronic myeloid leukemia, IM

Keywords

• cml
• leukemia
• imatinib
• resistance