Arsenic trioxide downregulates the expression of annexin II in bone marrow cells from patients with acute myelogenous leukemia.
BACKGROUND
Most patients with acute myelogenous leukemia (AML) suffer from disordered hemostasis. We have previously shown that annexin II (Ann II), a high-affinity co-receptor for plasminogen/tissue plasminogen activator, plays a central role in primary hyperfibrinolysis in patients with acute promyelocytic leukemia (APL). The expression of Ann II in cells from patients with major subtypes of AML and the effect of arsenic trioxide (As2O3) on Ann II expression in AML cells were investigated to determine whether As2O3-mediated downregulation of Ann II could restore hemostatic stability.


METHODS
A total of 103 patients (48 females and 55 males; age, 19 - 58 years) were included. Plasma samples were collected before and after treatment as well as after complete remission. Ann II and plasminogen activation were measured in leukemic cells during treatment with 1 micromol/L As2O3.


RESULTS
Before As2O3 treatment, Ann II mRNA expression (real-time PCR) was the highest in M3 cells (P < 0.05), higher in M5 cells than that in M1, M2, M4, and M6 cells (P < 0.001), and positively correlated with Ann II protein expression (flow cytometry) (r = 0.752, P < 0.01). Exposure for up to 120 hours to As2O3 (1 micromol/L) had no significant effect on Ann II protein in M1 and M2 leukemic cells, but decreased Ann II protein expression twofold within 48 hours of exposure in M3 cells (P < 0.05) and twofold within 96 hours in M5 cells (P < 0.05). The rate of plasmin generation was higher in APL, M5, and M4 cells than in M1, M2, and M6 cells.


CONCLUSIONS
As2O3 may reduce hyperfibrinolysis in AML by downregulation of Ann II. Furthermore, As2O3 affects more than one form of AML (APL, M4 and M5), suggesting its potential role in their management.
Department of Hematology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. zhangxh100@sina.com
Xiao-hui
XH
Zhang
Yu
Y
Hu
Li
L
Bao
Qian
Q
Jiang
Ling-hua
LH
Yang
Xi-jing
XJ
Lu
Mei
M
Hong
Ling-hui
LH
Xia
Tao
T
Guo
Guan-xin
GX
Shen
Hong-hu
HH
Zhu
Ting
T
Zhao
Shan-jun
SJ
Song
D000328:Adult; D017306:Annexin A2 / Q000378:metabolism*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D017306:Annexin A2; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide