Dynamic changes in the levels of sCD62L and SPARC in chronic myeloid leukaemia patients during imatinib treatment

J Clin Pharm Ther. 2022 Dec;47(12):2115-2129. doi: 10.1111/jcpt.13759. Epub 2022 Aug 23.

Abstract

What is known and objective: Chronic myeloid leukaemia (CML) microenvironment is responsible for resistance of leukaemic cells to tyrosine kinase inhibitor, altered adhesion, increased proliferation and leukaemic cells growth and survival through the secretion of many soluble molecules. We aimed at monitoring soluble L-selectin (sCD62L) and secreted protein acidic and rich in cysteine (SPARC) levels in chronic phase chronic myeloid leukaemia (CP-CML) patients and assessing the impact of imatinib on these parameters.

Methods: This prospective controlled clinical trial enrolled 35 subjects classified into two groups: control group included 10 healthy volunteers and CP-CML patients group included 25 newly diagnosed CP-CML patients received imatinib 400 mg once daily. sCD62L plasma levels, SPARC serum levels, breakpoint cluster region-Abelson1 (BCR-ABL1) %, complete blood count with differential, liver and kidney functions parameters were assessed at baseline and after 3 and 6 months of treatment.

Results and discussion: At baseline, sCD62L and SPARC were significantly elevated in CP-CML patients (p < 0.05) compared to control group. After 3 months of treatment, sCD62L was non-significantly decreased (p > 0.05), while surprisingly SPARC was significantly increased (p < 0.05) compared to baseline. Moreover, after 6 months of treatment, sCD62L was significantly decreased (p < 0.05) and SPARC was non-significantly decreased (p > 0.05) compared to baseline. In addition, sCD62L was significantly correlated with WBCs and neutrophils counts, while SPARC was significantly correlated with lymphocytes count at baseline and after 3 and 6 months of imatinib treatment.

What is new and conclusion: The elevated levels of sCD62L and SPARC at diagnosis in CP-CML patients could reflect their roles in CML pathogenesis and the dynamic changes in their levels during imatinib therapy might suppose additional mechanisms of action of imatinib beside inhibition of BCR-ABL. Furthermore, imatinib showed a significant impact on sCD62L and SPARC levels during treatment period.

Keywords: SPARC; chronic myeloid leukaemia; imatinib; sCD62L; soluble L-selectin.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Drug Resistance, Neoplasm
  • Humans
  • Imatinib Mesylate / pharmacology
  • Imatinib Mesylate / therapeutic use
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Osteonectin / therapeutic use
  • Prospective Studies
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines / therapeutic use
  • Tumor Microenvironment

Substances

  • Antineoplastic Agents
  • Imatinib Mesylate
  • Osteonectin
  • Protein Kinase Inhibitors
  • Pyrimidines
  • SPARC protein, human