Annexin II and Bleeding in Acute Promyelocytic Leukemia
Jill S. Menell, M.D., Gabriela M. Cesarman, M.D., Andrew T. Jacovina, B.S., Mary Ann McLaughlin, M.D., M.P.H., Emil A. Lev, Ph.D., and Katherine A. Hajjar, M.D.
Background Acute promyelocytic leukemia (APL) is associatedwith a hemorrhagic disorder of unknown cause that responds totreatment with all-trans-retinoic acid.
Methods We studied a newly described receptor for fibrinolyticproteins, annexin II, in cells from patients with APL or otherleukemias. We examined initial rates of in vitro generationof plasmin by tissue plasminogen activator (t-PA) in the presenceof APL cells that did or did not have the characteristic translocationof APL, t(15;17). We also determined the effect of all-trans-retinoicacid on the expression of annexin II and the generation of cell-surfaceplasmin.
Results The expression of annexin II, as detected by a fluorescein-taggedantibody, was greater on leukemic cells from patients with APLthan on other types of leukemic cells (mean fluorescence intensity,6.9 and 2.9, respectively; P<0.01). The t(15;17)-positiveAPL cells stimulated the generation of cell-surface, t-PA–dependentplasmin twice as efficiently as the t(15;17)-negative cells.This increase in plasmin was blocked by an anti–annexinII antibody and was induced by transfection of t(15;17)-negativecells with annexin II complementary DNA. The t(15;17)-positiveAPL cells contained abundant messenger RNA for annexin II, whichdisappeared through a transcriptional mechanism after treatmentwith all-trans-retinoic acid.
Conclusions Abnormally high levels of expression of annexinII on APL cells increase the production of plasmin, a fibrinolyticprotein. Overexpression of annexin II may be a mechanism forthe hemorrhagic complications of APL.
Source Information
From the Division of Hematology–Oncology, Departments of Pediatrics (J.S.M., A.T.J., E.A.L., K.A.H.) and Medicine (K.A.H.), Weill Medical College of Cornell University, New York; the Division of Hematology–Oncology, Department of Medicine, Instituto Nacional de la Nutricion Salvador Zubirán, Mexico City, Mexico (G.M.C.); and the Division of Cardiology, Department of Medicine, Mount Sinai Medical Center, New York (M.A.M.).
Address reprint requests to Dr. Menell at Columbia University, College of Physicians and Surgeons, 180 Ft. Washington Ave., HP5, New York, NY 10032, or at menellj{at}sjhmc.org.
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