Replication status in leukocytes of treated and untreated patients with polycythemia vera and essential thrombocytosis.
The replication status of malignant cells is usually asynchronous. However, to date the pattern of replication has not been studied in myeloproliferative disorders nor has the effect of chemotherapy been systematically evaluated. Therefore, we used fluorescence in situ hybridization to interphase nuclei in PHA-stimulated peripheral blood lymphocytes to examine replication timing of three alleles associated with the malignant process. The study group comprised hydroxyurea treated and untreated patients with essential thrombocytosis (ET) or polycythemia vera (PV). A significantly higher rate of the asynchronous pattern of replication in both treated and untreated patients was found as compared to healthy controls. The highest rate of asynchronous replication was observed in untreated patients. Also, the frequency of the two doublets pattern was significantly higher in the untreated group compared to the treated patients and to the control groups. In conclusion, patients with PV and ET have a higher rate of asynchronous pattern of replication. A possible correlation between disease activity and the pattern of replication is suggested. The effect of hydroxyurea on the pattern of replication is variable.
Amiel
Aliza
A
Genetic Institute, Meir Hospital, Sapir Medical Center, Kfar-Saba, Israel. alizaamiel@hotmail.com
Elis
Avishay
A
Maimon
Orit
O
Ellis
Martin
M
Herishano
Yair
Y
Gaber
Elena
E
Fejgin
Moshe D
MD
Lishner
Michael
M
D000328:Adult; D000368:Aged; D000986:Antisickling Agents / Q000494:pharmacology / Q000627:therapeutic use; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology / Q000627:therapeutic use; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011087:Polycythemia Vera / Q000188:drug therapy / Q000473:pathology*; D013922:Thrombocytosis / Q000188:drug therapy / Q000473:pathology*
D000986:Antisickling Agents; D019384:Nucleic Acid Synthesis Inhibitors; D006918:Hydroxyurea