title: All-trans-retinoic Acid differentially regulates proliferation of normal and leukemic B cells from different subsets of chronic lymphocytic leukemia.
abstract: All-trans-retinoic acid (ATRA) has been shown to modulate cell growth and differentiation in a variety of tumor cell types, but little is known regarding its precise role in regulation of leukemic B cells from different subsets of chronic lymphocytic leukemia (CLL). Previously, we showed that IL-21 significantly inhibits the CpG-mediated proliferation of CLL B cells in progressive compared to nonprogressive patients. In the present study, the effect of ATRA (10(-7) mol/L) on in vitro proliferation and apoptosis of B cells was investigated in 24 CLL patients and 8 normal subjects. Our results showed that ATRA markedly enhanced CpG-mediated proliferation of normal B cells, but it slightly inhibited CpG-induced proliferation of CLL B cells [stimulation index (SI): 105.6 vs. 14.7, P = 0.0001]. Although addition of IL-21 counteracted the proliferative effect of ATRA in normal B cells, it significantly enhanced the growth of tumor B cells in presence of CpG and ATRA. This stimulatory effect was restricted to nonprogressive and unmutated patients compared to progressive and mutated groups, respectively. Our results suggest that ATRA acts differentially on normal and CLL B cells and might have therapeutic implication in patients with progressive disease.
authors.affiliation: a Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran and Immunology Research Center, Medical School , Mashhad University of Medical Sciences , Mashhad , Iran.
authors.forename: Ghasem
authors.initials: G
authors.lastname: Ghalamfarsa
authors.forename: Farhad
authors.initials: F
authors.lastname: Jadidi-Niaragh
authors.forename: Mohammad Mehdi
authors.initials: MM
authors.lastname: Amiri
authors.forename: Seyed Mohsen
authors.initials: SM
authors.lastname: Razavi
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Saboor-Yaraghi
authors.forename: Fazel
authors.initials: F
authors.lastname: Shokri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007378:Interleukins / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D000098546:Interleukin-21
chemical_list: D000970:Antineoplastic Agents; C408982:CPG-oligonucleotide; D007378:Interleukins; D009838:Oligodeoxyribonucleotides; D014212:Tretinoin; D000098546:Interleukin-21