TY - JOUR
T1 - Clinical and cell biological features related to cellular drug resistance of childhood acute lymphoblastic leukemia cells
AU - Kaspers, G. J.L.
AU - Pieters, R.
AU - Van Zantwijk, C. H.
AU - Van Wering, E. R.
AU - Veerman, A. J.P.
N1 - Funding Information:
Acknowledgements Financially supported by the Dutch Cancer Society (IKA 89-06) and by the project VONK (VU Onderzoek Naar Kinderkanker). Computer equipment was provided by Olivetti Nederland B.V. The laboratory of the Dutch Childhood Leukemia Study Group (DCLSG) provided most of the patient samples. Board members of the DCLSG are H. Van Den Berg, M. V. A. Bruin, J. P. M. Bokkerink, P. J. Van Dijken, K. Hiihlen, W. A. Kamps, F. A. E. Nabben, A. Postma, J. A. Rammeloo, I. M. Risseeuw-Appel, A. Y. N. Schouten-Van Meeteren, G. A. M. De Vaan, E. Th. Van ‘t Veer-Korthof, A. J. P. Veerman, M. Van Weel-Sipman and R. S. Weening.
PY - 1995
Y1 - 1995
N2 - Several clinical and cell biological features, such as sex, age, leukemic cell burden, morphologic FAB type, and immunophenotype, have prognostic value in childhood acute lymphoblastic leukemia (ALL). The explanation for their prognostic significance is unclear, but might be related to cellular drug resistance. We prospectively studied the relation between the above mentioned features with resistance to 13 drugs in 144 childhood ALL samples obtained at initial diagnosis. The MTT assay was used for drug resistance testing. The interindividual differences in drug resistance were very large and exceeded those between the several subgroups. There was generally no significant relation between sex, leukemic cell burden, and FAB type with drug resistance. However, subgroups with a worse prognosis as defined by age (< 18 months and > 120 months at diagnosis) or immunophenotype (pro-B ALL and T-ALL) did show relatively resistant drug resistance profiles as compared to the subgroups with a better prognosis (age 18-120 months, common and pre-B ALL). Within the group of common and pre-B ALL and compared to the intermediate age-group, samples of the younger children were significantly more resistant to daunorubicin, mitoxantrone and teniposide, and samples of the older children were significantly more resistant to prednisolone and mercaptopurine. Pro-B ALL samples were significantly more resistant to I-asparaginase and thioguanine, and T-ALL samples were significantly more resistant to prednisolone, dexamethasone, I-asparaginase, vincristine, vindesine, daunorubicin, doxorubicin, teniposide, and ifosfamide, than the group of common and pre-B ALL cases. We conclude that the prognostic significance of age and immunophenotype in particular may be explained, at least partly, by its relation with resistance to certain drugs. The results of this study may be useful for future rational improvements of chemotherapeutic regimens in childhood ALL.
AB - Several clinical and cell biological features, such as sex, age, leukemic cell burden, morphologic FAB type, and immunophenotype, have prognostic value in childhood acute lymphoblastic leukemia (ALL). The explanation for their prognostic significance is unclear, but might be related to cellular drug resistance. We prospectively studied the relation between the above mentioned features with resistance to 13 drugs in 144 childhood ALL samples obtained at initial diagnosis. The MTT assay was used for drug resistance testing. The interindividual differences in drug resistance were very large and exceeded those between the several subgroups. There was generally no significant relation between sex, leukemic cell burden, and FAB type with drug resistance. However, subgroups with a worse prognosis as defined by age (< 18 months and > 120 months at diagnosis) or immunophenotype (pro-B ALL and T-ALL) did show relatively resistant drug resistance profiles as compared to the subgroups with a better prognosis (age 18-120 months, common and pre-B ALL). Within the group of common and pre-B ALL and compared to the intermediate age-group, samples of the younger children were significantly more resistant to daunorubicin, mitoxantrone and teniposide, and samples of the older children were significantly more resistant to prednisolone and mercaptopurine. Pro-B ALL samples were significantly more resistant to I-asparaginase and thioguanine, and T-ALL samples were significantly more resistant to prednisolone, dexamethasone, I-asparaginase, vincristine, vindesine, daunorubicin, doxorubicin, teniposide, and ifosfamide, than the group of common and pre-B ALL cases. We conclude that the prognostic significance of age and immunophenotype in particular may be explained, at least partly, by its relation with resistance to certain drugs. The results of this study may be useful for future rational improvements of chemotherapeutic regimens in childhood ALL.
KW - Acute lymphoblastic
KW - Age
KW - Childhood
KW - Drug resistance
KW - Immunophenotype
KW - Leukemia
KW - MTT assay
UR - http://www.scopus.com/inward/record.url?scp=0028825688&partnerID=8YFLogxK
U2 - 10.3109/10428199509112198
DO - 10.3109/10428199509112198
M3 - Article
C2 - 8590840
AN - SCOPUS:0028825688
SN - 1042-8194
VL - 19
SP - 407
EP - 416
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 5-6
ER -