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Published on: July 20, 2016
SOLUBLE CD150 ISOFORM LEVEL IN PLASMA OF CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS
I Gordiienko1, V Shcherbina1, L Shlapatska1
1R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the NAS of Ukraine, Kyiv, Ukraine.
Insights
Soluble CD150 (sCD150) is secreted by chronic lymphocytic leukemia (CLL) B cells. High plasma sCD150 levels correlate with better drug sensitivity in CLL patients.
Area of Science:
- Immunology
- Hematology
- Molecular Biology
Background:
- SLAMF1/CD150 plays a role in B cell signaling in chronic lymphocytic leukemia (CLL).
- Signaling can occur via homophilic CD150 binding or interaction with the soluble CD150 isoform (sCD150).
- The role of plasma sCD150 in CLL cell activation is not fully understood.
Purpose of the Study:
- To develop an ELISA for sCD150 quantification.
- To assess sCD150 levels in CLL patient plasma.
- To correlate sCD150 levels with B cell CD150 expression.
Main Methods:
- Analysis of plasma and peripheral blood mononuclear cells from 40 CLL patients.
- Development and application of an ELISA assay for sCD150.
- Ex vivo drug sensitivity and cell viability assays were performed.
Main Results:
- sCD150 was detected in all CLL plasma samples at varying levels.
- Low B cell surface CD150 expression correlated with high plasma sCD150.
- Elevated plasma sCD150 was linked to increased sensitivity to chemotherapy.
Conclusions:
- CLL B cells actively secrete sCD150, leading to its accumulation in plasma.
- Plasma sCD150 may contribute to the clinical variability observed in CLL.
- sCD150 levels could serve as a predictive biomarker for treatment response.
Background:
SLAMF1/CD150 is an active player in B cell signaling networks in chronic lymphocytic leukemia (CLL). CD150-mediated signaling initiates through a homophilic CD150 binding, which spans the adjacent cells, or the interaction with the soluble CD150 isoform (sCD150). The expression of sCD150 isoform at the mRNA and protein levels ex vivo was confirmed. However, it is unclear whether sCD150 isoform present in the blood plasma of CLL patients is a factor in the constitutive activation of CD150+ cells. The aim of this study was to develop an ELISA assay for the specific sCD150 evaluation and assess the sCD150 levels in the blood plasma of CLL patients with different CD150 expression on B cells.
Materials And Methods:
Blood plasma samples and peripheral blood mononuclear cells from 40 previously untreated CLL patients were analyzed. An ELISA method, ex vivo drug sensitivity assay, and a cell viability assay were used.
Results:
The sCD150 isoform was found in all studied plasma samples of CLL patients at different levels regardless of the cell surface CD150 expression status of B cells and sCD150 mRNA expression. CLL cases with low levels of the cell surface CD150 expression in B cells are characterized by high levels of sCD150 in blood plasma in contrast to the CLL cases with high cell surface CD150 expression on B cells. The elevated levels of sCD150 in blood plasma are associated with a better sensitivity of malignant B cells to cyclophosphamide and bendamustine.
Conclusions:
The sCD150 isoform is actively secreted by CLL B cells with its accumulation in blood plasma, which may be regarded as an additional factor in the CLL clinicopathologic variability.
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