Plasma Levels of Soluble CD86 Are an Independent Prognostic Marker in AML but Not MDS

Patton, William Nigel; Hock, Barry D.; Mckenzie, Judy L.; Haring, Lisa F.; Estey, Elihu H.; Albitar, Maher; Et Al

Blood 100(11): Abstract No. 2970


ISSN/ISBN: 0006-4971
Accession: 035508020

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Cell surface expression of CD86 (mCD86) provides a critical costimulatory signal in immune responses. However mCD86 expression by AML blasts is a marker of poor prognosis suggesting the presence of inhibitors of this pathway. The release of soluble forms of CD86 (sCD86) by malignant cells could provide a mechanism by which tumour cells inhibit immune responses. We have previously demonstrated that (1) sCD86 can be detected at ng/ml levels in normal plasma; (2) a proportion of AML patients have significantly elevated plasma sCD86 levels; (3) changes in sCD86 levels reflect remission/relapse status and (4) AML blasts express sCD86 transcript. These findings led us to analyse the prognostic significance of pre treatment plasma sCD86 levels in AML (n=57) and MDS (n=40) patients. Normal donors (n=52) had a median sCD86 level of 0.74 ng/ml (range 0.22-2.3) whilst a wider range of levels was observed in both MDS (median = 0.8 ng/ml, range 0.02-11.5) and AML (median =0.67, range 0.02-10.5) patients. No significant associations between sCD86 levels and other clinical and laboratory parameters were observed in MDS patients and sCD86 levels were not prognostically significant in these patients. However in AML, sCD86 levels correlated with high white cell count (P <0.0001) and high monocytes (P=0.0002). More importantly, higher levels of sCD86 were associated with shorter survival in AML patients when considered as a continuous variable (p=0.03). There was no significant difference in the sCD86 levels observed in AML patients with poor cytogenetics (-5, -7, 11q-, +8) compared to other patients. Multivariate analysis confirmed that sCD86 is an independent prognostic factor from cytogenetics (p=0.02). These results confirm that sCD86 levels are an independent prognostic factor in AML and suggest that sCD86 may have an important functional role in these patients. Furthermore, these results support the concept that MDS disease is biologically different from AML and may require a different therapeutic approach.