C-reactive protein (CRP) associated with higher risk patients with myelodysplastic syndromes (MDS)

Abstract

18009 Background: MDS and myeloma patients respond to many of the same therapeutic agents, suggesting a possible pathologic mechanism for both diseases. C-reactive protein (CRP) is an acute-phase protein produced by hepatocytes in response to tissue damage and inflammation under the transcriptional control of cytokines IL-6 and IL-1. Plasma CRP levels are a sensitive marker of inflammatory processes and are increased in patients with various cancers. CRP has been shown to bind and protect multiple myeloma cells from dexamethasone-induced apoptosis both in vitro and in vivo. CRP acts independently but in synergy with IL6, to promote survival and proliferation of myeloma. Increased expression of IL6 may be found in some patients with MDS suggesting that CRP may be a target of therapy in both diseases. We measured the serum concentrations of CRP in 94 MDS patients and 12 normal volunteers to see if levels correlated with clinical subtype as an initial step in exploring a common link between the two diseases. Methods: All patients and normal controls were consented according to IRB approved protocol. The standard immunochemical - turbidimetry method for CRP was used on the Ortho Vitros Fusion 5,1 instrument. The reference range for CRP measurements was 0.01-1.50 mg/dL. Results: Among 94 MDS patients, 36 had RA, 19 RARS, 27 RAEB, 9 RAEBt, 2 CMML and 1 AML. The IPSS score: 25 Low, 26 Int1, 24 Int2, 17 High and 2 unknown. Cytogenetics were normal in 47 and abnormal in 47. Higher than ULN CRP values were seen in 23 MDS cases (median 3.3 mg/dL, range 1.5–16.4 mg/dL) and 17/23 had either RAEB (6) or Int2/high risk disease. Normal controls had a median CRP of 0.27 mg/dL. Lower risk RA/RARS patients had 0.36 mg/dL and higher risk RAEB/RAEBt had 0.895mg/dL (p = 0.03). Similarly, according to IPSS, Low/Int1 had 0.395 mg/dL and Int2/High had 0.83 mg/dL (p = 0.05). Conclusion: We conclude that both sets of analyses indicate that higher CRP levels are associated with higher risk disease. The marrows of higher risk patients have decreasing numbers of apoptotic cells with increasing blast counts. The apoptotic protective role of CRP in these MDS remains to be elucidated. No significant financial relationships to disclose.