Clinical manifestations associated with the aberrant expression of the soluble granulocyte-macrophage colony-stimulating factor receptor in patients presenting with haematological malignancies

Abstract

The receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) can exist as both transmembrane (tmGMRα) and soluble (solGMRα) isoforms, and the latter, is a normal constituent of human plasma. We investigated if aberrant solGMRα expression occurs in haematopoietic malignancies and whether or not solGMRα expression levels correlated with clinical presentation. Compared with the normal population, patients with acute lymphoblastic leukaemia (ALL) had low levels of solGMRα whereas clonal disorders of the myeloid lineage demonstrated higher levels of solGMRα. Patients with acute myelogenous leukaemia (AML) and high levels of solGMRα presented with a distinct clinical picture. These patients were older, predominantly belonged to the M4 and M5 French-American-British (FAB) subtypes, and they had higher white blood cell counts at presentation including myeloid precursors and myeloblasts. They often presented with either unexplained lung infiltrates or hypoxia and lower rates of microbiologically defined infections. Elevated solGMRα levels were not associated with decreased relapse-free and overall survival in the AML population. On multivariate analysis, the correlation between elevated solGMRα levels and age, M4 and M5 FAB subtypes and decreased numbers of infections persisted. Our study is the first to describe that distinct clinical presentations are associated with aberrant solGMRα levels in haematological malignancies.