Common resistance mechanisms to nucleoside analogues in variants of the human erythroleukemic line K562.

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Dumontet C, Bauchu EC, Fabianowska K, Lepoivre M, Wyczechowska D, Bodin F, Rolland MO

Common resistance mechanisms to nucleoside analogues in variants of the human erythroleukemic line K562.

Adv Exp Med Biol. 1999;457:571-7.

PubMed ID

10500836 [ View in PubMed

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Abstract

Variants of the human K562 were developed against the nucleoside analogues cytosine arabinoside, 2 chlorodeoxyadenosine, fludarabine and gemcitabine. The resistant lines displayed a high degree of cross-resistance to all nucleoside analogues, with little or no cross resistance to other agents. There was a profound accumulation defect of the different nucleoside analogues in all of the variants. There was a strong overexpression of 5'nucleotidase, measured by rt-PCR and enzyme activity, in all resistant variants. There was a two fold increase of ribonucleotide reductase in the fludarabine resistant line and increased expression of purine nucleoside phosphorylase in the 2 chlorodeoxyadenosine selected line. Karyotypic analysis revealed the loss of a 6(q16;q22) deletion present in the parental line in all of the resistant lines. This portion of chromosome 6 has been shown to contain the gene for 5'nucleotidase. Early events in the transport and metabolism appear to be involved in the resistance mechanisms to nucleoside analogues and are responsible for broad cross resistance to this family of compounds.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Cladribine	Purine nucleoside phosphorylase	Protein	Humans	Yes	Inducer	Details