Variation in WNT genes expression in different subtypes of chronic lymphocytic leukemia.
The Wnt molecules are a family of secretory glycoproteins implicated in proliferation and differentiation of both normal and malignant cells. Despite extensive investigation of the WNT genes expression profile in various tumors, little is known about their expression in chronic lymphocytic leukemia (CLL). In this study, the expression profile of 14 WNT genes was investigated in a large number of Iranian patients with CLL. Semi-quantitative RT-PCR was performed on peripheral blood leukemic cells obtained from 62 patients with CLL. Peripheral blood mononuclear cells isolated from 11 age matched normal subjects served as control to determine baseline expression level of these genes. Our results have demonstrated significant up-regulation of WNT-3, WNT-4, WNT-5B, WNT-7B, WNT-9A, WNT-10A, and WNT-16B in patients with CLL compared to normal subjects (p < 0.05 to p < 0.0001). WNT gene expression analysis in different CLL subtypes showed a similar pattern of expression in progressive and indolent clinical subtypes. Over-expression of WNT-5A and WNT-9A genes was observed in patients with no mutation in their immunoglobulin (Ig) variable region heavy chain (Ig VH) genes compared to those with mutated Ig VH genes. Comparison between patients expressing VH1 (n = 9), VH3 (n = 40) and VH4 (n = 12) gene families, revealed down-regulation of WNT-3 and WNT-9A in VH3 positive patients. Our results indicate up-regulation of many members of the WNT gene family in CLL suggesting involvement of the Wnt canonical and/or noncanonical signaling pathways in CLL tumorigenesis.
Memarian
Ali
A
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Hojjat-Farsangi
Mohammad
M
Asgarian-Omran
Hossein
H
Younesi
Vahid
V
Jeddi-Tehrani
Mahmood
M
Sharifian
Ramazan Ali
RA
Khoshnoodi
Jalal
J
Razavi
Seyed Mohsen
SM
Rabbani
Hodjatallah
H
Shokri
Fazel
F
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000235:genetics*; D060508:Wnt3 Protein; D060528:Wnt4 Protein
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D020033:Protein Isoforms; C484142:WNT10A protein, human; C417262:WNT16 protein, human; C555507:WNT3 protein, human; C555581:WNT4 protein, human; C435831:WNT5B protein, human; C490675:WNT7B protein, human; C110670:WNT9A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060528:Wnt4 Protein