Cytarabine (AraC), an analogue of deoxycytidine, is the most effective cytotoxic agent in the treatment of acute myeloid leukemia (AML), which blocks DNA synthesis by inhibiting the function of DNA and RNA polymerases [1].
Cytarabine is incorporated into DNA, it blocks DNA synthesis by inhibiting the function of DNA and RNA polymerases. The most essential step in the AraC activation is phosphorylation into the monophosphate form, which is catalyzed by deoxycytidine kinase (dCK).
In AraC-sensitive rat leukemic cells, sole expression of inactive or spliced dCK forms make a cell resistant to the cytotoxic effects of AraC. It was reported that Ara-C also causes placental growth retardation, induce apoptosis and also impair cell proliferation in the zone of placental labyrinth. By injecting Ara-C into pregnant rats, the placentas were examined from 1 to 48h. the apoptosis of trophoblastic cells in the placental labyrinth zone increased from 3 h after the injecting and then peaked at 6 h and returned to control level at 48 h. Immunoreactivity of p53 protein in the placental labyrinth zone was significantly enhanced and peaked at 3 h after treatment, while no increase in p53 mRNA expression was detected by a reverse transcription polymerase chain reaction [1, 2].
A retrospective analysis was performed in 40 patients which treated with cytarabine 1000 mg/m2/day, mitoxantrone 8 mg/m2/day and etoposide 100 mg/m2/day for five days. 30% of remission rate and 11.2 months of median remission duration was got. In univariate analysis, compared to ≥second relapse (p = 0.02), patients in first relapse had improved overall survival [3].
References:
[1].Veuger MJT, Heemskerk MHM, Honders MW, et al. Functional role of alternatively spliced deoxycytidine kinase in sensitivity to cytarabine of acute myeloid leukemic cells. Blood, 2002, 99(4): 1373-1380.
[2].Yamauchi H, Katayama K, Ueno M, et al. Involvement of p53 in 1-beta-D-arabinofuranosylcytosine-induced trophoblastic cell apoptosis and impaired proliferation in rat placenta. Biology of Reproduction, 2004, 70(6): 1762-1767.
[3]. Liedtke M, Dunn T, Dinner S, et al. Salvage therapy with mitoxantrone, etoposide and cytarabine in relapsed or refractory acute lymphoblastic leukemia. Leukemia Research, 2014, 38(12): 1441-1445.
