Neoplasma Vol.52, p.74-78, 2005
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Title: In vitro sensitivity of leukemic cells to nucleoside derivatives
in childhood acute leukemias: good activity in leukemic relapses
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Author: J., STYCZYNSKI
; M., WYSOCKI
; R., DEBSKI
; K., CZYZEWSKI
; W., BALWIERZ
; E., JURASZEWSKA
; M., MATYSIAK
; I., MALINOWSKA
; E., STANCZAK
; D., SONTA-JAKIMCZYK
; T., SZCZEPANSKI
; J., WACHOWIAK
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Abstract: 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.
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Keywords: nucleoside analogues, leukemia, resistance, sensitivity
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Year: 2005, Volume: 52, Issue: |
Page From: 74, Page To: 78 |
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