Annexin II and bleeding in acute promyelocytic leukemia.
BACKGROUND
Acute promyelocytic leukemia (APL) is associated with a hemorrhagic disorder of unknown cause that responds to treatment with all-trans-retinoic acid.


METHODS
We studied a newly described receptor for fibrinolytic proteins, annexin II, in cells from patients with APL or other leukemias. We examined initial rates of in vitro generation of plasmin by tissue plasminogen activator (t-PA) in the presence of APL cells that did or did not have the characteristic translocation of APL, t(15;17). We also determined the effect of all-trans-retinoic acid on the expression of annexin II and the generation of cell-surface plasmin.


RESULTS
The expression of annexin II, as detected by a fluorescein-tagged antibody, was greater on leukemic cells from patients with APL than on other types of leukemic cells (mean fluorescence intensity, 6.9 and 2.9, respectively; P<0.01). The t(15;17)-positive APL cells stimulated the generation of cell-surface, t-PA-dependent plasmin twice as efficiently as the t(15;17)-negative cells. This increase in plasmin was blocked by an anti-annexin II antibody and was induced by transfection of t(15;17)-negative cells with annexin II complementary DNA. The t(15;17)-positive APL cells contained abundant messenger RNA for annexin II, which disappeared through a transcriptional mechanism after treatment with all-trans-retinoic acid.


CONCLUSIONS
Abnormally high levels of expression of annexin II on APL cells increase the production of plasmin, a fibrinolytic protein. Overexpression of annexin II may be a mechanism for the hemorrhagic complications of APL.
Menell
J S
JS
Department of Pediatrics, Weill Medical College of Cornell University, New York, NY, USA. menellj@sjhmc.org
Cesarman
G M
GM
Jacovina
A T
AT
McLaughlin
M A
MA
Lev
E A
EA
Hajjar
K A
KA
D000293:Adolescent; D000328:Adult; D017306:Annexin A2 / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000906:Antibodies / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005341:Fibrinolysin / Q000096:biosynthesis*; D005342:Fibrinolysis / Q000187:drug effects / Q000276:immunology; D006474:Hemorrhagic Disorders / Q000209:etiology; D006801:Humans; D007938:Leukemia / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014178:Translocation, Genetic; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017306:Annexin A2; D000906:Antibodies; D012333:RNA, Messenger; D014212:Tretinoin; D005341:Fibrinolysin