Apoptosis induction with fludarabine on freshly isolated chronic myeloid leukemia cells.
BACKGROUND
Fludarabine (FLU) is a fluorinated purine analogue with antineoplastic activity in lymphoproliferative malignancies. Recently, some in vitro reports have showed the effective role of FLU on the activation of apoptosis.


METHODS
The induction of programmed cell death (apoptosis) by fludarabine (FLU), an adenine nucleoside analogue, alpha-interferon (alpha-IFN), and FLU plus alpha-IFN was evaluated in vitro against freshly isolated, chronic-phase Ph1+ chronic myeloid leukemia (CML). Apoptosis was detected by electrophoresis gel of DNA oligonucleosomal fragments in 8 CML samples.


RESULTS
Only FLU and FLU plus alpha-IFN significantly activated apoptosis in all the samples, suggesting selective activity on CML cells. On the other hand, alpha-IFN alone did not activate programmed cell death.


CONCLUSIONS
Our data show apoptotic activity for FLU on CML cells. Programmed cell death may be suppressed in cells carrying the bcr-abl transcript, and FLU might remove this resistance in the neoplastic cell cycle. This preliminary report justifies using FLU in pilot clinical trials for chronic phase Ph1+ CML patients.
Zinzani
P L
PL
Istituto di Ematologia L. e A. Seràgnoli, Università degli Studi di Bologna, Italy.
Buzzi
M
M
Farabegoli
P
P
Martinelli
G
G
Tosi
P
P
Zuffa
E
E
Visani
G
G
Testoni
N
N
Salvucci
M
M
Bendandi
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002469:Cell Separation; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D014407:Tumor Cells, Cultured; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; D014740:Vidarabine; C024352:fludarabine