No preferential sensitivity of t(8;21) acute myeloid leukemias to cytosine arabinoside in vitro: is intensity of therapy or high dose Ara-C crucial for response?
Acute myeloid leukemia (AML) patients with core binding factor abnormalities [inv(16) or t(8;21)] have a relatively good prognosis, especially patients with inv(16) when treated with high-dose cytosine arabinoside (AraC) containing regimens, whereas in the case of t(8;21) evidences in favor of such regimen are contrasting. We previously demonstrated that blast cells from inv(16)-positive AML patients are characterized by an increased sensitivity to AraC with higher incorporation of 3H AraC into DNA and the increase of induced apoptosis in vitro. In the present study we tested the sensitivity of leukemic cells from 15 t(8;21)-positive AML patients to AraC and compared it with the results obtained from cells of 74 patients with inv(16), "intermediate" or "unfavourable" karyotype at diagnosis (for a total of 89 patients). The incorporation of 3H AraC into DNA in cells with t(8;21) was significantly lower than in cells with inv(16) (P = 0.02) or normal karyotype (P = 0.04). Interestingly, the incorporation of the drug into DNA in t(8;21) cells was similar to those with "unfavourable" karyotype. Furthermore, AraC induced apoptosis in t(8;21)-positive AML cells was not increased. These data suggest that the mechanism of response to chemotherapy for t(8;21)-positive cells is probably different then in AML cells with inv(16), underlining the possible importance for patients carrying the t(8;21) of repeated high-dose regimens and not necessarily of high-dose AraC based ones.
Visani
Giuseppe
G
Department of Hematology, H San Salvatore, Pesaro, Italy. gvisani@ospedalesansalvatore.it
Isidori
Alessandro
A
Grafone
Tiziana
T
Tosi
Patrizia
P
Santini
Valeria
V
Malagola
Michele
M
Martinelli
Giovanni
G
Piccaluga
Pier Paolo
PP
Gaziev
Djavid
D
Ottaviani
Emanuela
E
Sparaventi
Giovanni
G
Tura
Sante
S
D000208:Acute Disease; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics* / Q000648:ultrastructure; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics* / Q000648:ultrastructure; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004273:DNA, Neoplasm; D003561:Cytarabine