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

Abstract

Summary. The receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) can exist as both transmembrane (tmGMRa) and soluble (solGMRa) isoforms, and the latter, is a normal constituent of human plasma. We investigated if aberrant solGMRa expression occurs in haematopoietic malignancies and whether or not solGMRa expression levels correlated with clinical presentation. Compared with the normal population, patients with acute lymphoblastic leukaemia (ALL) had low levels of solGMRa whereas clonal disorders of the myeloid lineage demonstrated higher levels of solGMRa. Patients with acute myelogenous leukaemia (AML) and high levels of solGMRa presented with a distinct clinical picture. These patients were older, predominantly belonged to the M4 and M5 French-AmericanBritish (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 solGMRa levels were not associated with decreased relapse-free and overall survival in the AML population. On multivariate analysis, the correlation between elevated solGMRa 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 solGMRa levels in haematological malignancies.

Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia

“…30 Abnormalities of GM-CSF, IL-3 and their receptors have been most commonly associated with lymphoma and leukemia. 31,32 A previously unexplained (though replicated) epidemiologic finding in schizophrenia has been the reduced incidence of these two cancers in relatives of SCZ patients. 33,34 Similarly, an elevated level of GM-CSF in synovial fluid has been implicated in the inflammatory pathophysiology of rheumatoid arthritis (RA), 35 and SCZ patients have consistently demonstrated a reduced prevalence of RA.…”