[Effect of arsenic trioxide and daunorubicin on procoagulant activity of acute promyelocytic leukemia cells].
OBJECTIVE
To explore the effect of arsenic trioxide (ATO) and daunorubicin (DNR) on phosphatidylserine (PS) exposure and related procoagulant activity of acute promyelocytic leukemia (APL) cells.


METHODS
Mononuclear cell and neutrophil isolated from whole blood of 12 healthy volunteers were used as control group while APL cells obtained from 12 newly diagnosed APL patients at First Affiliated Hospital, Harbin Medical University from March 2007 to February 2009 were used as experimental group. APL cells were treated with 1 µmol/L ATO and 1 µmol/L DNR for 24 h. PS exposure of APL cells were measured by flow cytometry and confocal microscopy. And the related procoagulant activity was detected by the assays of coagulation time and coagulation factor formation. Lactadherin was used as a probe for PS exposure and anticoagulant on the cells of 12 APL patients.


RESULTS
ATO induced a decrease of PS exposure on APL cells by flow cytometry and no staining with lactadherin was observed under confocal microscopy. However, DNR induced the significantly elevated PS exposure and staining green with a rim pattern on membrane of APL cells was obtained. Coagulation time was (180 ± 25) s and (220 ± 41) s before and after treatment with ATO, respectively (P < 0.05). The formation of coagulation factors decreased after treatment with ATO (P < 0.05). While coagulation time was (180 ± 25) s and (80 ± 20) s before and after treatment with DNR, respectively (P < 0.05). The formation of coagulation factors increased after treatment with DNR (all P < 0.05). Lactadherin inhibited the procoagulant activities of DNR-treated APL cells (all P < 0.05).


CONCLUSIONS
Procoagulant activity is positively correlated with the exposed PS of APL cells. ATO and DNR inhibited and enhanced procoagulant activity with decreased and increased PS exposure, respectively.
Department of Hematology, First Affiliated Hospital, Harbin Medical University, Harbin 150001, China. shi73661@gmail.com
Jia-lan
JL
Shi
Jin-mei
JM
Li
Jin-xiao
JX
Hou
Feng-lin
FL
Cao
Shu-chuan
SC
Liu
Jin
J
Zhou
Chun-yan
CY
Gao
Jing
J
Wang
Xiao-yan
XY
Tan
Jia-nan
JN
Li
Yue
Y
Liu
Yan
Y
Liu
Rui-shuang
RS
Ma
Xue
X
Yang
D000328:Adult; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D003630:Daunorubicin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D014407:Tumor Cells, Cultured; D055815:Young Adult
D001152:Arsenicals; D010087:Oxides; D010718:Phosphatidylserines; D013925:Thromboplastin; D000077237:Arsenic Trioxide; D003630:Daunorubicin