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

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.

L-Selectin Expression is Influenced by Phosphatase Activity in Chronic Lymphocytic Leukemia.

BACKGROUND: Adhesion receptors have important role in cellular invasiveness and L-selectin is a primary determinant in the binding of chronic lymphocytic leukemia (CLL) cells to several glycated proteins on endothelial cells. We investigated L-selectin expression on CLL cells and explored the mechanisms that lead to their shedding. METHODS: Surface and soluble L-selectin expression levels were studied by flow cytometry and immunoassay, respectively. Magnetically isolated B-cells from patients and controls were investigated for total and protein phosphatase-2A activities. Flow cytometry of permeabilized cells was utilized for the determination of phosphorylated mitogen-activated protein kinase (pp38MAPK) and surface tumor necrosis factor alpha-converting enzyme expression (TACE). RESULTS: In CLL patients elevated absolute lymphocyte cell counts, high soluble and low surface L-selectin expression were observed. Similarly, TACE surface expression was significantly lower on B-CLL cells compared to normal B-cells. Both total phosphatase and protein phosphatase-2A activities were also significantly lower in B-CLL cells compared to normal B-cells and we found a consequently higher level of pp38 MAPK in B-CLL cells. Based on in vitro experiments a MAPK inhibitor could attenuate the phosphatase inhibitor's effect on L-selectin shedding. CONCLUSIONS: The lower phosphatase activity detectable in chronic lymphocytic leukemia, results in a downstream signaling cascade with subsequent reduction of surface L-selectin expression and this effect is mediated by enhanced phosphorylation of p38MAPK and an altered TACE expression. © 2019 The Authors. Cytometry Part B: Clinical Cytometry published by Wiley Periodicals, Inc. on behalf of International Clinical Cytometry Society.

High salivary soluble L-selectin and interleukin-7 levels in Asian Indian patients with primary Sjögren's syndrome.

In present study, we aimed to study salivary soluble L-selectin (sL-selectin), interleukin-7(IjL-7), and lymphotoxin-α levels in primary Sjögren's syndrome (pSS) and their clinical as well as serological correlations. pSS patients fulfilling either the American European Consensus Group (AECG) and/or the American college of Rheumatology (ACR) criteria were recruited. Age- and sex-matched hospital staff were recruited as healthy controls. Unstimulated saliva was collected by the spitting method; sL-selectin, IL-7, and lymphotoxin-α were measured in the saliva using commercial ELISA kits. Forty-three patients with pSS and 31 healthy controls were included in the study. Increased levels of sL-selectin and IL-7 were found in the saliva of patients as compared to controls. Lymphotoxin-α was undetectable in the saliva of pSS patients and controls. Salivary sL-selectin positively correlated with rheumatoid factor (r = 0.47; p < 0.003). No other variable including ESSDAI was significantly associated with salivary sL-selectin and IL-7 levels. Indian patients with primary Sjögren's syndrome have higher salivary sL-selectin and IL-7 levels than healthy controls.