Biochemical and cytokinetic characterization of leukemic cells: prediction of treatment results and early diagnosis of relapse.
Selected key-steps in the biochemical pathways of DNA-synthesis and cytokinetic parameters were measured in human bone marrow cells: Thymidine kinase (TK), incorporation of nucleosides (thymidine = dTR and deoxyuridine = dUR), % cells in DNA-synthesis-phase of the cell division cycle (%S). 26 normal marrow and a total of 369 marrow specimens from patients with acute leukemia were assayed either at first diagnosis, during remission or at relapse. A significant 5-fold increase of TK was found in leukemic cells, thus, being a suitable marker for follow-up of these patients. The sensitivity to detect a high TK at primary diagnosis of acute leukemia is 83%. An increase of TK during remission can indicate an imminent relapse before an increase of blast cells can be detected in the bone marrow. The incorporation-rates of dTR and dUR were also significantly increased in leukemic cells. Patients who did not achieve complete remission after induction treatment had higher incorporation-rates. In contrast to the enhanced biochemical activity of DNA-metabolism, %S-phase-cells were significant lower in leukemic cell populations. %S-phase cells did not correlate with treatment results. An inhibition of DNA synthesis, estimated by the incorporation rates of dTR and dUR for more than 50% during the first 3-4 days after start of induction treatment corresponds with cytoreduction in the leukemic bone marrow which does not predict complete remission in all cases.
Wilmanns
W
W
Medical Clinic III, Ludwig-Maximilians-Universität Munich, West Germany.
Sauer
H
H
Pelka-Fleischer
R
R
Twardzik
L
L
Vehling-Kaiser
U
U
D004247:DNA / Q000096:biosynthesis*; D006801:Humans; D007399:Interphase; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012008:Recurrence; D013937:Thymidine Kinase / Q000032:analysis
D004247:DNA; D013937:Thymidine Kinase