title: Differential regulation of B-cell proliferation by IL21 in different subsets of chronic lymphocytic leukemia.
abstract: Interleukin-21 (IL21) plays an important role in B-cell proliferation, survival and differentiation. Contrary to its stimulatory effect in normal B cells, it has been shown that it induces pro-apoptotic effect in leukemic B cells from CLL patients. Little is known regarding the biological function of IL21 in leukemic B cells from progressive and non-progressive CLL patients. In the present study, the proliferative effect of IL21 in combination with TLR9 agonist (CpG) was investigated in B cells isolated from 24 CLL patients and eight normal subjects by radioactive thymidine incorporation assay. B cells were enriched from peripheral blood mononuclear cells by negative selection using magnetic beads (MACS) and immunophenotyped by flow cytometry. Our results showed that IL21 enhanced the proliferative effects of CpG in both normal and leukemic B cells, though no significant differences were observed between CLL patients and healthy controls. Comparison between different subsets of patients revealed that while the combination of IL21 and CpG significantly inhibited the proliferation of B cells from progressive compared to non-progressive patients (p=0.001), it enhanced proliferation of leukemic B cells from IGHV mutated compared to unmutated patients (p=0.001). The inhibitory effect of IL21 on proliferation of normal and leukemic cells was found to be apoptosis-independent. Our findings suggest differential effects of IL21 in different subsets of CLL patients and suggest its potential therapeutic implication in patients with a more progressive disease.
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ghasem
authors.initials: G
authors.lastname: Ghalamfarsa
authors.forename: Farhad
authors.initials: F
authors.lastname: Jadidi-Niaragh
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hojjat-Farsangi
authors.forename: Hossein
authors.initials: H
authors.lastname: Asgarian-Omran
authors.forename: Mehdi
authors.initials: M
authors.lastname: Yousefi
authors.forename: Fathollah
authors.initials: F
authors.lastname: Tahmasebi
authors.forename: Jalal
authors.initials: J
authors.lastname: Khoshnoodi
authors.forename: Seyed Mohsen
authors.initials: SM
authors.lastname: Razavi
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Saboor-Yaraghi
authors.forename: Hodjatallah
authors.initials: H
authors.lastname: Rabbani
authors.forename: Mahmood
authors.initials: M
authors.lastname: Jeddi-Tehrani
authors.forename: Fazel
authors.initials: F
authors.lastname: Shokri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000473:pathology*; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D007378:Interleukins / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D000098546:Interleukin-21
chemical_list: C408982:CPG-oligonucleotide; D007378:Interleukins; D009838:Oligodeoxyribonucleotides; D000098546:Interleukin-21