Summary. Resistant variants of the human leukaemic line K562 were developed using selection with the deoxynucleoside analogues cytosine arabinoside, 2-chlorodeoxyadenosine, udarabine and gemcitabine. The resistant lines displayed a high degree of cross resistance to all deoxynucleoside analogues, with little or no cross resistance to other agents. There was a profound accumulation defect of all nucleoside analogues in the resistant variants but no signi®cant defect in nucleoside transport in any of the variants. 5H nucleotidase activity was strongly increased and deoxycytidine kinase activity was moderately reduced in all of the resistant variants, resulting in reduced accumulation of triphosphate analogues. In addition a deletion in one of the alleles of the deoxycytidine kinase was detected in thē udarabine-resistant line. Ribonucleotide reductase activity was found to be strongly increased in the gemcitabineselected line and purine nucleoside phosphorylase was increased in the 2-chlorodeoxyadenosine-selected line. Free nucleotide pools were increased in the 2-chlorodeoxyadenosineselected line. There was no expression of the mdr1 gene by the resistant lines. Karyotypic analysis and FISH experiments using a 6q21 speci®c probe showed alterations in the 6(q16-q22) region which contains the 5 H -nucleotidase gene. Early events in the activation and degradation of deoxynucleoside analogues appear to constitute common mechanisms of resistance to these compounds.

The clinical relevance of the IgD measurement for the diagnosis of MKD in our population appears as poor, as reflected by likelihood ratios which are both close to 1.