In vitro sensitivity and cross-resistance to deoxynucleoside analogs in childhood acute leukemia.
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In vitro sensitivity and cross-resistance to deoxynucleoside analogs in childhood acute leukemia. / Hubeek, Isabelle; Peters, Godefridus J; Broekhuizen, Richard; Zwaan, Christian M; Kaaijk, Patricia; Wering, van; Elisabeth, S; Gibson, Brenda E S; Janka-Schaub, Gritta; Janka-Schaub, Gritta E; Boer, den; Monique, L; Pieters, Rob; Kaspers, Gertjan J L.
in: HAEMATOLOGICA, Jahrgang 91, Nr. 1, 1, 2006, S. 17-23.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - In vitro sensitivity and cross-resistance to deoxynucleoside analogs in childhood acute leukemia.
AU - Hubeek, Isabelle
AU - Peters, Godefridus J
AU - Broekhuizen, Richard
AU - Zwaan, Christian M
AU - Kaaijk, Patricia
AU - Wering, van
AU - Elisabeth, S
AU - Gibson, Brenda E S
AU - Janka-Schaub, Gritta
AU - Janka-Schaub, Gritta E
AU - Boer, den
AU - Monique, L
AU - Pieters, Rob
AU - Kaspers, Gertjan J L
PY - 2006
Y1 - 2006
N2 - BACKGROUND AND OBJECTIVES: Cytarabine (ara-C) is a key drug in the treatment of acute leukemia. Resistance to ara-C might be circumvented by the use of other deoxynucleoside analogs. DESIGN AND METHODS: Using the MTT assay, we determined in vitro sensitivity and cross-resistance to deoxynucleoside analogs in 362 acute leukemia samples from untreated children and 32 normal bone marrow mononuclear cell samples. RESULTS: Normal bone marrow samples were significantly more resistant to ara-C, cladribine and fludarabine than were acute myeloid leukemia (AML) samples and significantly more resistant to ara-C and fludarabine than were acute lymphoblastic leukemia (ALL) samples. The only drug to which AML samples were more sensitive in vitro than ALL was cladribine. AML FAB M5 was significantly more sensitive in vitro to ara-C and cladribine than FAB M1/2 or FAB M4. T-ALL was significantly more resistant to cladribine than B-cell precursor ALL. A paired analysis of 60 AML and 99 ALL samples demonstrated significant cross-resistance between all four deoxynucleoside analogs. Cross-resistance was also observed between ara-C and etoposide (Rp=0.54, p
AB - BACKGROUND AND OBJECTIVES: Cytarabine (ara-C) is a key drug in the treatment of acute leukemia. Resistance to ara-C might be circumvented by the use of other deoxynucleoside analogs. DESIGN AND METHODS: Using the MTT assay, we determined in vitro sensitivity and cross-resistance to deoxynucleoside analogs in 362 acute leukemia samples from untreated children and 32 normal bone marrow mononuclear cell samples. RESULTS: Normal bone marrow samples were significantly more resistant to ara-C, cladribine and fludarabine than were acute myeloid leukemia (AML) samples and significantly more resistant to ara-C and fludarabine than were acute lymphoblastic leukemia (ALL) samples. The only drug to which AML samples were more sensitive in vitro than ALL was cladribine. AML FAB M5 was significantly more sensitive in vitro to ara-C and cladribine than FAB M1/2 or FAB M4. T-ALL was significantly more resistant to cladribine than B-cell precursor ALL. A paired analysis of 60 AML and 99 ALL samples demonstrated significant cross-resistance between all four deoxynucleoside analogs. Cross-resistance was also observed between ara-C and etoposide (Rp=0.54, p
M3 - SCORING: Zeitschriftenaufsatz
VL - 91
SP - 17
EP - 23
JO - HAEMATOLOGICA
JF - HAEMATOLOGICA
SN - 0390-6078
IS - 1
M1 - 1
ER -
