IL-7 receptor is expressed on adult pre-B-cell acute lymphoblastic leukemia and other B-cell derived neoplasms and correlates with expression of proliferation and survival markers.
The interleukin (IL)-7 receptor (IL-7R) is expressed on human pre-B but not mature B-cells. We hypothesised that aberrant expression of IL-7R contributes to B-cell oncogenesis. Surface expression of IL-7R components CD127 and CD132, and intracellular Ki-67 and Bcl-2 were examined by flow cytometry on peripheral blood or bone marrow mononuclear cells (PBMC; BMMC) from patients with B-cell derived neoplasms, chronic human immunodeficiency virus type-1 (HIV-1) infection alone, or healthy volunteers. Plasma IL-7, IL-2, IL-4, IL-6, IL-10, IL-21, TNF-alpha, IFN-gamma and BAFF were measured by enzyme-linked immuno-sorbent assay or bead array. The effects of exogenous IL-7 on PBMC and BMMC were examined. CD127 expression was elevated in pre-B-cell acute lymphoblastic leukemia (pre-B-ALL) and in some cases of Non-Hodgkin's Lymphoma (B-NHL). Plasma IL-7 levels were higher in pre-B-ALL, B-cell chronic lymphocytic leukemia (B-CLL) and HIV-1 associated B-NHL (HIV-B-NHL) compared with control groups. CD127+ pre-B-ALL cells had higher expression of Ki-67, Bcl-2 and CD132 than CD127- counterparts. Unlike T-lineage cells, CD127+ pre-B-ALL cells did not down-regulate CD127 in response to exogenous IL-7. Patients with B-cell derived neoplasms had elevated circulating IL-10 and decreased BAFF. These findings support a role for the IL-7/IL-7R system in B-cell oncogenesis.
Sasson
Sarah C
SC
National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia. s.sasson@cfi.unsw.edu.au
Smith
Sandy
S
Seddiki
Nabila
N
Zaunders
John J
JJ
Bryant
Adam
A
Koelsch
Kersten K
KK
Weatherall
Christopher
C
Munier
Mee-Ling
ML
McGinley
Ciara
C
Yeung
Julie
J
Mulligan
Stephen P
SP
Moore
John
J
Cooper
David A
DA
Milliken
Sam
S
Kelleher
Anthony D
AD
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D015925:Cryopreservation; D016207:Cytokines / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000276:immunology*; D012189:Retrospective Studies; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000473:pathology
D014408:Biomarkers, Tumor; D016207:Cytokines; C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D020395:Receptors, Interleukin-7