Abstract: PB1766
Type: Publication Only
Background
Chemokines and their receptors are involved in the regulation of cell recruitment, survival, proliferation, and trafficking, all these processes crucial in the pathogenesis of chronic lymphocytic leukemia (CLL). Comprehensive profiling of chemokine receptors in CLL and its subgroups according prognostic relevance is missing.
Aims
To characterize the chemokine expression pattern in CLL patients and subgroups according to clinical course and cytogenetic aberrations.
Methods
We studied the gene expression pattern of 16 canonical and 4 atypical chemokine receptors in peripheral blood mononuclear cells (PBMC) of CLL patients (n=88) and healthy subjects (n=34) by using SmartChip quantitative RT-PCR (WaferGen Bio-systems). The expression of CXCR3, CXCR4, CXCR5, CXCR7, and CCR7 was confirmed by flow cytometry.
Results
Among deregulated receptors, 5 receptors (CCR7, CCR10, CXCR3, CXCR4, CXCR5) were up-regulated and 9 receptors (CCR2-CCR6, CCR8, CCRL2, CXCR1, CXCR2) down-regulated in CLL; the expression of others did not differ between CLL and controls (P>0.05). In patients with del(17p) associated with a poor prognosis, we observed higher mRNA levels of CXCR6, CXCR7 and CCR10 comparing to del(13q). On protein level, the percentage of neoplastic B cells positive for CXCR4, CXCR5, and CCR7 was higher and percentage of CXCR7 lower than on normal B cells (P<0.05). In patients with CLL a marked increase in MFI of CXCR4 (P<0.001) and CCR7 (P<0.001) on CLL cells was detected comparing to healthy subjects.
Conclusion
Our results provide a complete picture of expression patterns of chemokine receptors in PBMC of CLL patients and prognostically relevant subgroups. Further studies are needed to clarify how chemokine receptor network affects neoplastic development and progression.
Grant support: MZ ČR VES16-32339A, IGA_LF_2017_009, IGA_LF_2017_001.
Session topic: 5. Chronic lymphocytic leukemia and related disorders - Biology
Keyword(s): Expression profiling, Chronic Lymphocytic Leukemia, Chemokine receptor, Chemokine