Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P33527 (ABCC1)
 1,164 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Contradictory data have been reported about the prognostic value of myeloid antigen co-expression (My+) in childhood acute lymphoblastic leukaemia (ALL). In the present study the methyl thiazol tetrazoliumbromide (MTT) assay was used to compare the in vitro cytotoxicity of 14 drugs between 60 My+ (CD13+ and/or CD33+) and 107 My- ALL children at initial diagnosis. P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), major vault protein/lung resistance protein (LRP) and the intracellular daunorubicin concentration were studied by flow cytometry. My+ ALL samples were significantly more resistant, i.e. between 1.1- and 2.9-fold, to daunorubicin, doxorubicin, idarubicin, mitoxantrone, vincristine, 6-thioguanine, 6-mercaptopurine, teniposide, etoposide and ifosfamide compared with My- ALL samples. My- and My+ ALL did not significantly differ in sensitivity to prednisolone, dexamethasone, L-asparaginase and cytarabine. Comparable results were found when only common and preB ALL cases were analysed. Drug resistance in My+ ALL was not related to increased expression of P-gp, MRP or LRP compared with My- ALL (ratio My+/My-:P-gp 0.8, MRP 1.0, LRP 1.1). Accumulation and retention of daunorubicin did not significantly differ between My- and My+ ALL cells (ratio My+/My-: accumulation 1.2, retention 1.3). Therefore the nature of drug resistance in My+ ALL remains unknown. The lack of prognostic value for My+ in childhood ALL may be explained by the responsiveness of My+ ALL to glucocorticoids, L-asparaginase and cytarabine. In addition, the currently intensive treatment regimens may apply drug doses which are simply high enough to overcome the mild resistance to anthracyclines, mitoxantrone, vincristine, thiopurines, epipodophyllotoxins and ifosfamide in childhood My+ ALL.
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PMID:Myeloid antigen co-expression in childhood acute lymphoblastic leukaemia: relationship with in vitro drug resistance. 1055 96

In vitro resistance to anthracyclines is related to a poor prognosis in childhood acute lymphoblastic leukemia (ALL), but the underlying mechanisms are poorly understood. Using flow cytometry, we studied the contribution of daunorubicin (DNR) accumulation and retention, cell size, expression of the major vault protein/lung resistance protein (LRP), P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) to the cytotoxicity of DNR (by MTT assay) in childhood ALL. The accumulated and retained DNR content was not related to the degree of DNR resistance, nor did the content differ between 53 initial and 20 relapse ALL samples (P >0. 05), although the latter were median two-fold more resistant to DNR (P = 0.004). Leukemic cell volume correlated with resistance to the anthracyclines DNR (Rs 0.32, P = 0.012) and idarubicin (Rs 0.46, P = 0.011) but not to other classes of drugs such as prednisolone, vincristine, L-asparaginase and etoposide. Relapsed patients had 1. 5-fold larger cells than patients at initial diagnosis of ALL (P = 0. 001). After cell volume correction, the intracellular DNR concentration was lower in relapsed compared with initial ALL cells (eg 60 min accumulation, P = 0.003). Moreover, the intracellular DNR concentration inversely correlated with DNR resistance, both in the accumulation (Rs -0.44, P < 0.001) and retention (Rs -0.33, P = 0. 016) test condition. The accumulated DNR concentration inversely correlated with expression of LRP (Rs -0.36, P = 0.012) but not with P-gp and MRP. Expression of LRP, but not of P-gp and MRP, significantly correlated with DNR resistance in childhood ALL (Rs 0. 33, P = 0.03). In conclusion, the intracellular DNR concentration and the expression level of LRP may contribute to DNR resistance in childhood ALL. The strength of the correlations also indicates that resistance to anthracyclines can not be explained by one single mechanism.
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PMID:Relationship between the intracellular daunorubicin concentration, expression of major vault protein/lung resistance protein and resistance to anthracyclines in childhood acute lymphoblastic leukemia. 1060 24