Efficacy of N-acetylcysteine and all-trans retinoic acid in restoring in vitro effective hemopoiesis in myelodysplastic syndromes.
We evaluated the in vitro effect on clonogenic potential (CFU-GM) and apoptosis in myelodysplastic syndromes (MDS) progenitors of an anti-oxidant (N-acetylcysteine, NAC) and/or a differentiating (all-trans retinoic acid, ATRA) agent. NAC significantly reduced apoptosis, both NAC and ATRA induced an increase in CFU-GM, but NAC seemed to be particularly effective in the high risk (HR) MDS. NAC + ATRA conferred a significant advantage in terms of CFU-GM with respect to NAC and ATRA alone. Tumor Necrosis Factor-alpha (TNF-alpha) levels decreased after incubation with NAC in the MDS samples. This study shows that ineffective hemopoiesis in MDS could benefit from both NAC and ATRA, suggesting that anti-oxidant treatment may play a role in guaranteeing MDS cell survival, predisposing them towards differentiation.
Cortelezzi
A
A
Servizio Autonomo di Ematologia Diagnostica, Ospedale Maggiore Policlinico IRCCS, Milan, Italy. cortelez@polic.cilea.it
Cattaneo
C
C
Sarina
B
B
Cristiani
S
S
Pomati
M
M
Silvestris
I
I
Motta
M
M
Ibatici
A
A
Gornati
G
G
Volpe
A D
AD
Maiolo
A T
AT
D000111:Acetylcysteine / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000473:pathology*; D014212:Tretinoin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin; D000111:Acetylcysteine