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Reversal of drug‐resistance by cyclosporin‐A in a patient with acute myelocytic leukaemia
Author(s) -
Sonneveld Pieter,
Nooter Kees
Publication year - 1990
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1990.tb02650.x
Subject(s) - daunorubicin , cytarabine , clone (java method) , clonogenic assay , medicine , flow cytometry , in vitro , pharmacology , bone marrow , drug resistance , chemotherapy , intracellular , immunology , myeloid , leukemia , biology , dna , biochemistry , microbiology and biotechnology , genetics
Summary The emergence of resistant leukaemia in a patient with acute myeloid leukaemia (AML) was evaluated during clinical progression of the disease. At relapse, a decrease of the intracellular accumulation of daunorubicin (DNR) as determined by real time flow cytometry was associated with a relative overexpression of RNA encoding for the multidrug resistance phenotype (MDR 1 ), and by a decreased in vitro sensitivity to DNR of clonogenic AML cells (IC 50 0.8‐3.4 μ m ). Intracellular DNR accumulation and in vitro DNR sensitivity could be completely restored by adding cyclosporin‐A (3 μ m ) to the cells. At progressive relapse the patient was treated with re‐induction therapy (DNR 30 mg/m 2 x 3. cytarabine 200 mg/m 2 x 7) to which cyclosporin‐A was added (Cy‐A 4 mg/kg twice daily for 3 d, 2.5 mg/kg twice daily for 2 d). which resulted in elimination of the MDR 1 positive AML cells with restoration of the original DNR accumulation and in vitro sensitivity. After 12 weeks the resistant clone reappeared in the blood and bone marrow.