Characteristic proinflammatory serum cytokine profiles in patients with B-Cell chronic lymphocytic leukemia Meeting Abstract


Authors: Harding, J. J.; Yeh, R.; Nikhamin, Y.; Frattini, M.; Lamanna, N.; Jurcic, J. G.; Heaney, M.; Brentjens, R.
Abstract Title: Characteristic proinflammatory serum cytokine profiles in patients with B-Cell chronic lymphocytic leukemia
Meeting Title: 52nd Annual Meeting of the American Society of Hematology (ASH)
Abstract: BACKGROUND: Cytokines are posited to play a critical regulatory role on the survival of the B-cell neoplastic clone in Chronic Lymphocytic Leukemia (CLL). AIM: The primary goals of this study were 1) to define additional relevant cytokines, growth factors and chemokines in CLL pathophysiology and 2) to correlate abnormal cytokine levels with disease stage, relevant hematological data and multiple prognostic factors. METHODS: A novel bead-based protein array system was employed to simultaneously;measure 38 proinflammatory cytokines in the sera of CLL patients (N=116) and healthy age and-sex matched controls (N=30). These results were correlated with Rai stage, beta 2-microglobulin Level, LDH, CD38 expression and cytogenetic abnormalities. RESULTS: We first confirmed previous observations that TNF alpha, IL-1 alpha, IL-1RA, IL-10, sIL-2R alpha, VEGF and sCD40 ligand are significantly elevated in patients with CLL as compared with healthy controls. Expanding on the current literature, we demonstrated perturbations in an additional 15 serum cytokines in affected individuals. Compared to healthy. controls, CLL patients had an increase in serum levels of IL-3 (p=0.002), IL-7 (p=0.008), INF-2 alpha (p < 0.0001), MCP-1 (p < 0.0001), MIP-1 beta, (p=0.002), MDC (p < 0.0001), Fractakine (p < 0.0001), EGF (p < 0.0001), FGF-2 (p < 0.0001), GRO (p < 0.0001), Eotaxin (p < 0.0001) and FLT-3 ligand (p < 0.000I). Patients with CLL also exhibited significantly lower levels of INF-gamma. (p < 0.01), IL-6 (p < 0.005) and IL-8 (p < 0.002) when compared to healthy individuals. Advanced Rai stage and high risk chromosomal abnormalities (del I 1q and del 17p) strongly correlated with higher serum levels of TNFa, soluble IL-2R alpha, IL-10, MCP-1, MIP-1 alpha, MIP-1 beta and IP-10. Finally, serum levels of TNF alpha, MIP-1 alpha and MIP- 1 beta correlated with other adverse prognostic markers, including total white blood cell count, serum beta 2-microglobulin and LDH levels as well as CD38 expression. CONCLUSION: We have demonstrated numerous previously unrecognized cytokine abnormalities in patients with CLL and described a unique cytokine Signature associated with advanced disease. Supported by the current understanding of cytokine biology and CLL pathophysiology, our observations suggest an important regulatory role for hematopoietic cytokines, such as IL-3 and IL-7, in promulgating survival of the aberrant B-cell clone. Likewise, the profoundly high levels of chemokines (i.e. MCP-1, MIP- 1 alpha, MIP-1 beta, IP-10) and their association with high risk prognostic factors argue for their role in sustaining the neoplastic microenvironment. Finally, the altered levels of IL-10, IL-6 and INF-gamma observed in patients with CLL likely contribute to the immunosuppressive phenotype of the disease state.
Journal Title: Blood
Volume: 116
Issue: 21
Meeting Dates: 2010 Dec 4-7
Meeting Location: Orlando, FL
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2010-11-19
Start Page: 1480
Language: English
ACCESSION: BIOSIS:PREV201100426136
PROVIDER: biosis
PUBMED: 22276300
Notes: --- - Poster Session - Meeting Abstract: 3595 - 52nd Annual Meeting of the American-Society-of-Hematology (ASH) - Orlando, FL, USA - December 04 -07, 2010 - Amer Society of Hematology - "Source: Biosis"