TY - JOUR
T1 - Cellular drug resistance in childhood acute myeloid leukemia is related to chromosomal abnormalities
AU - Zwaan, Christian M.
AU - Kaspers, Gertjan J.L.
AU - Pieters, Rob
AU - Hählen, Karel
AU - Huismans, Dieuwke R.
AU - Zimmermann, Martin
AU - Harbott, Jochen
AU - Slater, Rosalyn M.
AU - Creutzig, Ursala
AU - Veerman, Anjo J.P.
PY - 2002/11/1
Y1 - 2002/11/1
N2 - Specific cytogenetic abnormalities predict prognosis in childhood acute myeloid leukemia (AML). However, it is unknown why they are predictive and whether this is related to drug resistance. We previously reported that Down syndrome (DS) AML was associated with favorable resistance profiles. Here, we successfully analyzed drug resistance and (cyto-) genetic abnormalities of 109 untreated childhood AML samples using the 4-day total cell-kill methyl-thiazol tetrazolium (MTT) assay. Patients were classified according to the genetic abnormalities in the leukemic cells: t(8;21), inv(16), t(15;17), t(9;11), other 11q23 translocations, abnormalities of chromosome 5/7, trisomy 8 alone, normal karyotype, single random, and multiple (defined as 2 or more) abnormalities. The DS AML samples were excluded from the subgroup analysis. Samples with chromosome 5/7 abnormalities were median 3.9-fold (P = .01) more resistant to cytarabine than other AML samples. The t(9;11) samples were more sensitive to cytarabine (median 2.9-fold, P= .002), etoposide (13.1-fold, P = .001), the anthracyclines (2.9- to 8.0-fold, P < .01), and 2-chlorodeoxyadenosine (10.0-fold, P= .002) than other AML samples. The trisomy 8 and t(15;17) groups were too small for meaningful analysis. All other genetic subgroups did not show specific resistance profiles. Overall, we found no differences in drug resistance in samples taken at diagnosis between patients remaining in continuous complete remission (CCR) versus the refractory/relapsed patients. Within several genetic subgroups, however, relapsed/refractory patients were more cytarabine resistant when compared with patients remaining in CCR, but numbers were small and the results were not significant. We conclude that some, but not all, cytogenetic subgroups in childhood AML display specific drug-resistance profiles.
AB - Specific cytogenetic abnormalities predict prognosis in childhood acute myeloid leukemia (AML). However, it is unknown why they are predictive and whether this is related to drug resistance. We previously reported that Down syndrome (DS) AML was associated with favorable resistance profiles. Here, we successfully analyzed drug resistance and (cyto-) genetic abnormalities of 109 untreated childhood AML samples using the 4-day total cell-kill methyl-thiazol tetrazolium (MTT) assay. Patients were classified according to the genetic abnormalities in the leukemic cells: t(8;21), inv(16), t(15;17), t(9;11), other 11q23 translocations, abnormalities of chromosome 5/7, trisomy 8 alone, normal karyotype, single random, and multiple (defined as 2 or more) abnormalities. The DS AML samples were excluded from the subgroup analysis. Samples with chromosome 5/7 abnormalities were median 3.9-fold (P = .01) more resistant to cytarabine than other AML samples. The t(9;11) samples were more sensitive to cytarabine (median 2.9-fold, P= .002), etoposide (13.1-fold, P = .001), the anthracyclines (2.9- to 8.0-fold, P < .01), and 2-chlorodeoxyadenosine (10.0-fold, P= .002) than other AML samples. The trisomy 8 and t(15;17) groups were too small for meaningful analysis. All other genetic subgroups did not show specific resistance profiles. Overall, we found no differences in drug resistance in samples taken at diagnosis between patients remaining in continuous complete remission (CCR) versus the refractory/relapsed patients. Within several genetic subgroups, however, relapsed/refractory patients were more cytarabine resistant when compared with patients remaining in CCR, but numbers were small and the results were not significant. We conclude that some, but not all, cytogenetic subgroups in childhood AML display specific drug-resistance profiles.
UR - http://www.scopus.com/inward/record.url?scp=0036838528&partnerID=8YFLogxK
U2 - 10.1182/blood.V100.9.3352
DO - 10.1182/blood.V100.9.3352
M3 - Article
C2 - 12384437
AN - SCOPUS:0036838528
SN - 0006-4971
VL - 100
SP - 3352
EP - 3360
JO - Blood
JF - Blood
IS - 9
ER -