FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 340:994-1004 April 1, 1999 Number 13 Next

	Full Text PDF Editorial by Rand, J. H. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

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.

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.

Full Text of this Article

This article has been cited by other articles:

• He, K.-L., Deora, A. B., Xiong, H., Ling, Q., Weksler, B. B., Niesvizky, R., Hajjar, K. A. (2008). Endothelial Cell Annexin A2 Regulates Polyubiquitination and Degradation of Its Binding Partner S100A10/p11. J. Biol. Chem. 283: 19192-19200 [Abstract] [Full Text]  
• Hastie, C., Masters, J. R., Moss, S. E., Naaby-Hansen, S. (2008). Interferon-{gamma} Reduces Cell Surface Expression of Annexin 2 and Suppresses the Invasive Capacity of Prostate Cancer Cells. J. Biol. Chem. 283: 12595-12603 [Abstract] [Full Text]  
• Bhattacharjee, G., Ahamed, J., Pawlinski, R., Liu, C., Mackman, N., Ruf, W., Edgington, T. S. (2008). Factor Xa Binding to Annexin 2 Mediates Signal Transduction via Protease-Activated Receptor 1. Circ. Res. 102: 457-464 [Abstract] [Full Text]  
• Jung, Y., Wang, J., Song, J., Shiozawa, Y., Wang, J., Havens, A., Wang, Z., Sun, Y.-X., Emerson, S. G., Krebsbach, P. H., Taichman, R. S. (2007). Annexin II expressed by osteoblasts and endothelial cells regulates stem cell adhesion, homing, and engraftment following transplantation. Blood 110: 82-90 [Abstract] [Full Text]  
• Ortiz-Zapater, E., Peiro, S., Roda, O., Corominas, J. M., Aguilar, S., Ampurdanes, C., Real, F. X., Navarro, P. (2007). Tissue Plasminogen Activator Induces Pancreatic Cancer Cell Proliferation by a Non-Catalytic Mechanism That Requires Extracellular Signal-Regulated Kinase 1/2 Activation through Epidermal Growth Factor Receptor and Annexin A2. Am. J. Pathol. 170: 1573-1584 [Abstract] [Full Text]  
• Frances, R., Tumang, J. R., Rothstein, T. L. (2007). Extreme skewing of annexin II and S100A6 expression identified by proteomic analysis of peritoneal B-1 cells. Int Immunol 19: 59-65 [Abstract] [Full Text]  
• Kwaan, H. C. (2007). Double Hazard of Thrombophilia and Bleeding in Leukemia. ASH Education Book 2007: 151-157 [Abstract] [Full Text]  
• Cesarman-Maus, G., Rios-Luna, N. P., Deora, A. B., Huang, B., Villa, R., Cravioto, M. d. C., Alarcon-Segovia, D., Sanchez-Guerrero, J., Hajjar, K. A. (2006). Autoantibodies against the fibrinolytic receptor, annexin 2, in antiphospholipid syndrome. Blood 107: 4375-4382 [Abstract] [Full Text]  
• Stein, T., Price, K. N., Morris, J. S., Heath, V. J., Ferrier, R. K., Bell, A. K., Pringle, M.-A., Villadsen, R., Petersen, O. W., Sauter, G., Bryson, G., Mallon, E. A., Gusterson, B. A. (2005). Annexin A8 Is Up-Regulated During Mouse Mammary Gland Involution and Predicts Poor Survival in Breast Cancer. Clin. Cancer Res. 11: 6872-6879 [Abstract] [Full Text]  
• Gveric, D., Herrera, B. M., Cuzner, M. L. (2005). tPA Receptors and the Fibrinolytic Response in Multiple Sclerosis Lesions. Am. J. Pathol. 166: 1143-1151 [Abstract] [Full Text]  
• Deora, A. B., Kreitzer, G., Jacovina, A. T., Hajjar, K. A. (2004). An Annexin 2 Phosphorylation Switch Mediates p11-dependent Translocation of Annexin 2 to the Cell Surface. J. Biol. Chem. 279: 43411-43418 [Abstract] [Full Text]  
• Diaz, V M, Hurtado, M, Thomson, T M, Reventos, J, Paciucci, R (2004). Specific interaction of tissue-type plasminogen activator (t-PA) with annexin II on the membrane of pancreatic cancer cells activates plasminogen and promotes invasion in vitro. Gut 53: 993-1000 [Abstract] [Full Text]  
• Rescher, U., Gerke, V. (2004). Annexins - unique membrane binding proteins with diverse functions. J. Cell Sci. 117: 2631-2639 [Abstract] [Full Text]  
• Lei, H., Romeo, G., Kazlauskas, A. (2004). Heat Shock Protein 90{alpha}-Dependent Translocation of Annexin II to the Surface of Endothelial Cells Modulates Plasmin Activity in the Diabetic Rat Aorta. Circ. Res. 94: 902-909 [Abstract] [Full Text]  
• Smith, K. S. (2004). "Annexing" acute leukemias. Blood 103: 2869-2870 [Full Text]  
• Matsunaga, T., Inaba, T., Matsui, H., Okuya, M., Miyajima, A., Inukai, T., Funabiki, T., Endo, M., Look, A. T., Kurosawa, H. (2004). Regulation of annexin II by cytokine-initiated signaling pathways and E2A-HLF oncoprotein. Blood 103: 3185-3191 [Abstract] [Full Text]  
• Filipenko, N. R., MacLeod, T. J., Yoon, C.-S., Waisman, D. M. (2004). Annexin A2 Is a Novel RNA-binding Protein. J. Biol. Chem. 279: 8723-8731 [Abstract] [Full Text]  
• Brownstein, C., Deora, A. B., Jacovina, A. T., Weintraub, R., Gertler, M., Khan, K. M. F., Falcone, D. J., Hajjar, K. A. (2004). Annexin II mediates plasminogen-dependent matrix invasion by human monocytes: enhanced expression by macrophages. Blood 103: 317-324 [Abstract] [Full Text]  
• Peterson, E. A., Sutherland, M. R., Nesheim, M. E., Pryzdial, E. L. G. (2003). Thrombin induces endothelial cell-surface exposure of the plasminogen receptor annexin 2. J. Cell Sci. 116: 2399-2408 [Abstract] [Full Text]  
• Gerke, V., Moss, S. E. (2002). Annexins: From Structure to Function. Physiol. Rev. 82: 331-371 [Abstract] [Full Text]  
• BROWNSTEIN, C., FALCONE, D. J., JACOVINA, A., HAJJAR, K. A. (2001). Annexin II: A Mediator of Cell Surface-Specific Plasmin Generation. Ann. N. Y. Acad. Sci. 947: 143-156 [Abstract] [Full Text]  
• Brichory, F. M., Misek, D. E., Yim, A.-M., Krause, M. C., Giordano, T. J., Beer, D. G., Hanash, S. M. (2001). An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer. Proc. Natl. Acad. Sci. USA 98: 9824-9829 [Abstract] [Full Text]  
• Soignet, S. L. (2001). Clinical Experience of Arsenic Trioxide in Relapsed Acute Promyelocytic Leukemia. The Oncologist 6: 11-16 [Abstract] [Full Text]  
• Eberhard, D. A., Karns, L. R., VandenBerg, S. R., Creutz, C. E. (2001). Control of the nuclear-cytoplasmic partitioning of annexin II by a nuclear export signal and by p11 binding. J. Cell Sci. 114: 3155-3166 [Abstract] [Full Text]  
• Sainty, D., Liso, V., Cantu-Rajnoldi, A., Head, D., Mozziconacci, M.-J., Arnoulet, C., Benattar, L., Fenu, S., Mancini, M., Duchayne, E., Mahon, F.-X., Gutierrez, N., Birg, F., Biondi, A., Grimwade, D., Lafage-Pochitaloff, M., Hagemeijer, A., Flandrin, G. (2000). A new morphologic classification system for acute promyelocytic leukemia distinguishes cases with underlying PLZF/RARA gene rearrangements. Blood 96: 1287-1296 [Abstract] [Full Text]  
• DREWS, R. E., WEINBERGER, S. E. (2000). Thrombocytopenic Disorders in Critically Ill Patients. Am. J. Respir. Crit. Care Med. 162: 347-351 [Full Text]  
• HAJJAR, K. A., ACHARYA, S. S. (2000). Annexin II and Regulation of Cell Surface Fibrinolysis. Ann. N. Y. Acad. Sci. 902: 265-271 [Abstract] [Full Text]  
• Rand, J. H. (1999). "Annexinopathies" -- A New Class of Diseases. NEJM 340: 1035-1036 [Full Text]  
• Jacovina, A. T., Zhong, F., Khazanova, E., Lev, E., Deora, A. B., Hajjar, K. A. (2001). Neuritogenesis and the Nerve Growth Factor-induced Differentiation of PC-12 Cells Requires Annexin II-mediated Plasmin Generation. J. Biol. Chem. 276: 49350-49358 [Abstract] [Full Text]