Fludarabine-induced apoptosis in CD19+/CD5+B-CLL cells is a direct and nurse-like-cell independent effect.
B-cell chronic lymphocytic leukemia (B-CLL) is a hematological malignancy characterized by the accumulation of mature CD5+ B lymphocytes with a defective apoptosis. A subset of blood monocyte-derived adherent cells generated in vitro protects B-CLL cells from apoptosis playing a role as nurse-like cells (NLCs). Fludarabine (9-beta-D-arabinofuranosyl-2-fluoroadenine; F-ara-A) is an adenine nucleoside analog used to treat B-CLL. To gain insight into the mechanisms implicated in the antitumoral effect of fludarabine in B-CLL cells, we performed cross-cultures with B-CLL cells and NLCs treated and untreated with fludarabine. Our results showed that fludarabine blocked the development of NLCs and induced apoptosis in these cells when they were present in culture. Moreover, CD19+/CD5+B-CLL cells treated with fludarabine underwent apoptosis and this event was not related with the presence of NLCs whether treated or not with fludarabine. In conclusion, apoptosis induced by fludarabine in CD19+/CD5+B-CLL cells was due to a direct effect on these cells and not due to its effect in the NLCs.
Martinez-Lostao
Luis
L
Immunology Department, Hospital de Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.
Briones
Javier
J
Martinez-Gallo
Monica
M
Forné
Ignasi
I
Sierra
Jordi
J
Rodriguez-Sanchez
Jose Luis
JL
Juarez
Candido
C
D000368:Aged; D017304:Annexin A5 / Q000494:pharmacology; D018941:Antigens, CD19 / Q000096:biosynthesis*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D018956:CD5 Antigens / Q000096:biosynthesis*; D016923:Cell Death; D002470:Cell Survival; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D015448:Leukemia, B-Cell / Q000188:drug therapy* / Q000473:pathology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D013997:Time Factors; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D017304:Annexin A5; D018941:Antigens, CD19; D000970:Antineoplastic Agents; D018956:CD5 Antigens; D014740:Vidarabine; C024352:fludarabine