Phosphorylation of 2-chlorodeoxyadenosine (CdA) in extracts of peripheral blood mononuclear cells of leukaemic patients.
2-Chlorodeoxyadenosine (CdA) is an antileukaemic agent used in treatment of hairy cell leukaemia (HCL) and chronic lymphocytic leukaemia of B- and T-cell type (B-CLL and T-CLL). The aim of this study was to elucidate the interpatient variability of CdA phosphorylation and its relation to response to CdA treatment. In extracts of peripheral blood mononuclear cells of patients with B-CLL (n = 39), CdA phosphorylation was significantly higher than in HCL (n = 19) when calculated per protein (391 +/- 155 pmol CdA phosphorylated/mg protein/min versus 288 +/- 166 pmol/mg/min, P < 0.001), but was the same when calculated per cell (12 +/- 5.9 pmol/10(6) cells/min versus 14 +/- 5.9 pmol/10(6) cells/min) due to a larger cell volume in HCL. In T-CLL (n = 6), CdA phosphorylation was significantly lower than in B-CLL, both when calculated per protein (128 +/- 68 pmol/mg/min, P < 0.001) or per cell (5.7 +/- 2.7 pmol/10(6) cells/min, P < 0.05). This low CdA phosphorylation in T-CLL was unexpected because normal B- and T-lymphocytes contain equal amounts of CdA phosphorylation. With B-CLL, 21 patients who responded (complete and partial response) to CdA treatment showed a significantly higher CdA phosphorylation than 13 patients not responding to CdA treatment (456 +/- 170 pmol/mg/min versus 309 +/- 97 pmol/mg/min, P < 0.01). We conclude that the level of CdA phosphorylation is correlated with the response of leukaemias to CdA treatment.
Arnér
E S
ES
Department of Medical Biochemistry and Biophysics, Medical Nobel Institute, Karolinska Institutet, Stockholm, Sweden.
Spasokoukotskaja
T
T
Juliusson
G
G
Liliemark
J
J
Eriksson
S
S
D017338:Cladribine / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D007943:Leukemia, Hairy Cell / Q000097:blood / Q000188:drug therapy*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000188:drug therapy; D015461:Leukemia, Prolymphocytic, T-Cell / Q000097:blood / Q000188:drug therapy; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D010766:Phosphorylation
D017338:Cladribine