Chemokine Plasma Concentration in Patients with B-Cell Chronic Lymphocytic Leukemia.
Authors: Toro Juan J. , Ochoa-Bayona Leonel , Ahuja Seema S. , Quinones Marlon P. , Lee Shuko , Estrada Carlos A. , Freytes Cesar O. 
Published: April 2020

Background: The natural history of B-chronic lymphocytic leukemia (B-CLL) is not explained entirely by intrinsic defects of the neoplastic cell, but also is influenced by microenvironmental signals. Selected microenvironmental stimuli confer B-CLL cells a growth advantage and an extended survival. There is increasing evidence that chemokines are implicated in the neoplastic transformation and accumulation of cells. B-CLL cells are exposed to a complex pattern of signals that, through a gradient of chemokine concentrations, has been implicated in the pathogenesis of this disease allowing the B-cells to avoid apoptosis and proliferate. However, the specific array of chemokines is unknown. Chemokines are divided into two major subfamilies on the basis of the arrangement of the two N-terminal cysteine residues, CXC (where X is any amino acid) and CC. Two other classes of chemokines have been described: lymphotactin (C) and fractalkine (CX3C)

Purpose: To define the array of chemokines that may promote the survival/proliferation of B-CLL cells

Methods: We collected a detailed clinical history and screened the plasma of 45 patients with B-CLL and 20 sex-matched and aged-adjusted control subjects with an array of 9 chemokines that included members of the CXC family (ENA-78 and IL-8); the CC family (MCP-1, MDC, MIP-1a, MIP-1b, eotaxin and RANTES); and a member of the C family (lymphotactin). Measurements were performed using a multiplex assay based on Luminex technology. The performance characteristics of these tests were validated by Rules-Based Medicine, Inc. Essentially, this multiple assay measures proteins in a manner similar to standard sandwich ELISA.

Results: We found that compared with controls, B-CLL patients have significantly higher plasma levels of the CC chemokines [MCP-1 (p=0.0229), MIP-1a (p=0.001), and MDC (p=0.0183)] and significantly lower plasma levels of eotaxin (p=0.004). Likewise, plasma levels of the C chemokine lymphotactin (p=0.0002) also were significantly higher. In contrast, there were no significant differences in the plasma levels of the CXC chemokines analyzed. These associations were not explained by differences in disease stage or presence of co-morbidities such as hypertension, dyslipidemias, smoking, diabetes mellitus, deep venous thrombosis, coronary artery disease, cerebrovascular accident, asthma, or skin cancer. Only the CC chemokine MIP-1a (p=0.0273) was found to be significantly higher in patients who received treatment for B-CLL than in those who did not

Conclusions: Patients with B-CLL have significantly higher plasma levels of 3 CC chemokines (MCP-1, MIP-1a, MDC) than controls. However, they also have significantly lower plasma levels of eotaxin and significantly higher plasma levels of the C chemokine lymphotactin. No significant differences were seen in the levels of the CXC chemokines assessed. Further studies are necessary to define the cellular source of these chemokines and to determine the correlation between the plasma levels of these molecules and B-CLL progression and prognosis.