title: 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 (tmGMRalpha) and soluble (solGMRalpha) isoforms, and the latter, is a normal constituent of human plasma. We investigated if aberrant solGMRalpha expression occurs in haematopoietic malignancies and whether or not solGMRalpha expression levels correlated with clinical presentation. Compared with the normal population, patients with acute lymphoblastic leukaemia (ALL) had low levels of solGMRalpha whereas clonal disorders of the myeloid lineage demonstrated higher levels of solGMRalpha. Patients with acute myelogenous leukaemia (AML) and high levels of solGMRalpha 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 solGMRalpha levels were not associated with decreased relapse-free and overall survival in the AML population. On multivariate analysis, the correlation between elevated solGMRalpha 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 solGMRalpha levels in haematological malignancies.
authors.affiliation: Department of Medical Oncology, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Ontario, Canada.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Trus
authors.forename: Louise
authors.initials: L
authors.lastname: Bordeleau
authors.forename: Carin
authors.initials: C
authors.lastname: Pihl
authors.forename: Allison
authors.initials: A
authors.lastname: McGeer
authors.forename: Jay
authors.initials: J
authors.lastname: Prevost
authors.forename: Mark D
authors.initials: MD
authors.lastname: Minden
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Brown
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000097:blood; D007140:Immunoglobulin Fab Fragments / Q000097:blood; D007938:Leukemia / Q000097:blood*; D015470:Leukemia, Myeloid, Acute / Q000097:blood; D007958:Leukocyte Count; D008171:Lung Diseases / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009894:Opportunistic Infections / Q000097:blood; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood*; D015996:Survival Rate
chemical_list: D007140:Immunoglobulin Fab Fragments; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor