Clinical Pharmacy Department, Faculty of Pharmacy, Al Salam University in Egypt, Kafr El-Zayat, Egypt.
Medical Oncology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
J Clin Pharm Ther. 2022 Dec;47(12):2115-2129. doi: 10.1111/jcpt.13759. Epub 2022 Aug 23.
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.
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.
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.
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.
慢性髓性白血病(CML)微环境是导致白血病细胞对酪氨酸激酶抑制剂耐药、改变黏附性、增加增殖以及白血病细胞生长和存活的原因,其通过分泌许多可溶性分子来实现。我们旨在监测慢性期慢性髓性白血病(CP-CML)患者中可溶性 L-选择素(sCD62L)和富含半胱氨酸的酸性分泌蛋白(SPARC)的水平,并评估伊马替尼对这些参数的影响。
本前瞻性对照临床试验纳入了 35 名受试者,分为两组:对照组包括 10 名健康志愿者,CP-CML 患者组包括 25 名新诊断的 CP-CML 患者,每天接受 400mg 伊马替尼治疗。在基线和治疗 3 个月和 6 个月后,评估 sCD62L 血浆水平、SPARC 血清水平、BCR-ABL1%、全血细胞计数和分类、肝肾功能参数。
在基线时,CP-CML 患者的 sCD62L 和 SPARC 显著升高(p<0.05)。治疗 3 个月后,sCD62L 无显著降低(p>0.05),而 SPARC 却显著升高(p<0.05)。此外,治疗 6 个月后,sCD62L 显著降低(p<0.05),SPARC 无显著降低(p>0.05)。此外,sCD62L 与白细胞和中性粒细胞计数显著相关,而 SPARC 与基线时和伊马替尼治疗 3 个月和 6 个月后的淋巴细胞计数显著相关。
CP-CML 患者在诊断时 sCD62L 和 SPARC 的升高水平可能反映了它们在 CML 发病机制中的作用,并且在伊马替尼治疗期间它们水平的动态变化可能假设了伊马替尼除了抑制 BCR-ABL 之外的其他作用机制。此外,伊马替尼在治疗期间对 sCD62L 和 SPARC 水平有显著影响。