In vitro sensitivity of leukemic cells to nucleoside derivatives in childhood acute leukemias: good activity in leukemic relapses.
Nucleoside analogues such as fludarabine and cladribine are used in therapy of indolent lymphomas and leukemias in adults, while cytarabine is used mainly in protocols for acute leukemias. Mechanisms of their activity is based on inhibition of enzymes involved in DNA, RNA and protein synthesis. The objective of the study was the analysis of in vitro cellular drug sensitivity in childhood acute lymphoblastic (ALL) and myeloid (AML) leukemia. Isolated leukemic cells obtained from 264 patients, including 152 initial ALL, 45 relapsed ALL, 54 initial AML and 13 relapsed AML were tested for cytotoxicity for fludarabine, cladribine, and cytarabine by the MTT assay. Drug concentration lethal to 50% of tested cells was regarded as a value of drug resistance. Three tested nucleoside analogues showed highest cytotoxicity against initial ALL samples. Samples of relapsed ALL and initial AML were more resistant than ALL de novo ones. Unexpectedly, no differences were observed between initial and relapsed AML samples for all tested drugs, what suggests that nucleoside analogues are active drugs in relapsed AML, which is commonly regarded as a resistant disease. All tested drugs presented significant cross-resistance in each of analyzed subgroups. In summary, tested nucleoside analogues presented relatively good activity against childhood leukemias at relapse stage.
Styczynski
J
J
Department of Pediatric Hematology and Oncology, Collegium Medicum Bydgoszcz UMK, Bydgoszcz 85-094, Poland. jstyczynski@cm.umk.pl
Wysocki
M
M
Debski
R
R
Czyzewski
K
K
Balwierz
W
W
Juraszewska
E
E
Matysiak
M
M
Malinowska
I
I
Stanczak
E
E
Sońta-Jakimczyk
D
D
Szczepanski
T
T
Wachowiak
J
J
Konatkowska
B
B
Balcerska
A
A
Ploszynska
A
A
Kowalczyk
J
J
Stefaniak
J
J
Badowska
W
W
Wieczorek
M
M
Olejnik
I
I
Krawczuk-Rybak
M
M
Kuzmicz
M
M
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death; D002648:Child; D002675:Child, Preschool; D017338:Cladribine / Q000494:pharmacology*; D003561:Cytarabine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000473:pathology*; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D012008:Recurrence; D014407:Tumor Cells, Cultured; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D003561:Cytarabine; D017338:Cladribine; D014740:Vidarabine; C024352:fludarabine