Relationship of oxidative stress in the resistance to imatinib in Tunisian patients with chronic myeloid leukemia: A retrospective study

J Clin Lab Anal. 2020 Feb;34(2):e23050. doi: 10.1002/jcla.23050. Epub 2019 Oct 16.

Abstract

Background: This work aimed to evaluate oxidative stress in chronic myeloid leukemia (CML) patients treated with tunisian (IM) vs controls and in CML patients with resistance to IM vs patients without resistance to IM.

Methods: The study included 40 CML patients and 34 controls. Of 40 patients with CML, 26 patients were developed in resistance to IM. The oxidant/antioxidant markers were evaluated by spectrophotometric methods for all used samples.

Results: For CML patients, increased malondialdehyde (MDA) and advanced oxidation protein products (AOPP) levels were found compared to controls (P < .001; P = .01). Higher catalase (CAT) activity (P = .048) and lower superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, reduced Glutathione (GSH) and vitamin C levels were found in CML patients (P < .001). The comparison between the resistant vs no-resistant CML patients revealed higher MDA level (P = .02) and CAT and SOD activities in IM-resistant patients (P = .04, P = .03). GPx activity was reduced (P = .04). Furthermore, increased mean ratio of MDA/GSH, MDA/GPx, and SOD/(GPx + CAT) was found in IM-resistant patients as compared with no-resistant (P = .01, P = .01, P = .035). The mean ratio of GPx/GSH in the IM-resistant CML patients was lower than in IM no-resistant one (P = .039). For IM-resistant patients, we found negative correlation between MDA level and the ratio SOD/(CAT + GPx) (r = -0.46, P = .002); and positive correlation between SOD and (CAT + GPx) activities (r = 0.38, P = .06) and between GSH level and GPx activity (r = 0.53, P = .01).

Conclusions: Our results have shown a highly disturbed oxidative profile in IM-resistant CML patients as compared to no-resistant. The H2 O2 has a key role in the resistance to IM treatment.

Keywords: chronic myeloid leukemia; imatinib resistance; oxidative stress.

MeSH terms

  • Adult
  • Advanced Oxidation Protein Products / blood
  • Antineoplastic Agents / pharmacology*
  • Antioxidants / metabolism
  • Ascorbic Acid / blood
  • Case-Control Studies
  • Drug Resistance, Neoplasm / drug effects
  • Enzymes / blood
  • Female
  • Glutathione / blood
  • Humans
  • Imatinib Mesylate / pharmacology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Male
  • Malondialdehyde / blood
  • Middle Aged
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Treatment Outcome
  • Tunisia

Substances

  • Advanced Oxidation Protein Products
  • Antineoplastic Agents
  • Antioxidants
  • Enzymes
  • Malondialdehyde
  • Imatinib Mesylate
  • Glutathione
  • Ascorbic Acid