Annexin II and bleeding in acute promyelocytic leukemia

Background Acute promyelocytic leukemia (APL) is associated with a hemorrha gic disorder of unknown cause that responds to treatment with all trans-ret inoic acid. Methods We studied a newly described receptor for fibrinolytic proteins, an nexin II, in cells from patients with APL or other leukemias. We examined i nitial rates of in vitro generation of plasmin by tissue plasminogen activa tor (t-PA) in the presence of APL cells that did or did not have the charac teristic translocation of APL, t(15;17). We also determined the effect of a ll-trans-retinoic acid on the expression of annexin II and the generation o f cell-surface plasmin. Results The expression of annexin II, as detected by a fluorescein-tagged a ntibody, was greater on leukemic cells from patients with APL than on other types of leukemic cells (mean fluorescence intensity, 6.9 and 2.9, respect ively; P<0.01). The t(15;17)-positive APL cells stimulated the generation o f 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 a nnexin II complementary DNA. The t(15;17)positive APL cells contained abund ant messenger RNA for annexin II, which disappeared through a transcription al 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. (N Engl J Med 1999;340:994-1004,) (C)1999, Massachusetts Medical Society.