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

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.

The Bone Marrow Immune Microenvironment in CML: Treatment Responses, Treatment-Free Remission, and Therapeutic Vulnerabilities

“…Additionally, a shift in focus to maintaining long-term TFR stresses the need to eliminate MRD and the BCR::ABL1 + LSC in CML. Newer evidence sCD62L PB plasma Marker/putative predictor of response to TKI T-cell surface CD62L also interrelated with sCD62L and can predict responses [55,56]…”

“…Previous reports suggested CML LSCs were more dependent on L-selectin (CD62L) for BM homing and disease engraftment [54]. Soluble CD62L is elevated in CP-CML patients and reduced following imatinib treatment [55], suggesting it may have value as a marker of treatment response. In addition, soluble and T cell expression of CD62L may predict responses to TKIs in CML [56], indicating this marker may be more related to T cell responses than the CML cells themselves.…”