The impact of all-trans-retinoic acid on the coagulopathy of acute promyelocytic leukemia.

نویسندگان

  • T Barbui
  • G Finazzi
  • A Falanga
چکیده

ACUTE PROMYELOCYTIC leukemia (APL) is a distinct subtype of acute myelogenous leukemia (AML), identified by the French-American-British classification as AML-M31 and cytogenetically characterized by the balanced reciprocal translocation between chromosomes 15 and 17. Patients with the common hypergranular type of APL are most often leukopenic. However, a more aggressive form of APL, characterized by marked hyperleukocytosis and scarcely granulated blasts with bilobed or kidney-shaped nuclei, is described as the microgranular variant (M3v) and accounts for 25% of APL cases.2,3 The disease typically presents with a life-threatening hemorrhagic diathesis, which is worsened by cytotoxic chemotherapy. Recent studies report an incidence of early hemorrhagic deaths of about 10% to 20% in APL.4-7 In M3v APL the hemostatic disturbance and the inherent risk of early hemorrhagic death are particularly elevated.8 Improving the hemorrhagic complications is an important task in this disease, which shows an otherwise relatively favorable prognosis.9 The use of all-trans-retinoic acid (ATRA) for the remission induction therapy of APL has raised the complete remission (CR) rate to greater than 90%.6-8,10 ATRA promotes the terminal differentiation of leukemic promyelocytes. In these cells the fusion of the nuclear retinoic acid receptor (RARa) gene on chromosome 17 with part of the PML gene on chromosome 15 results in the expression of a chimeric PML/RARa protein, which is involved in both the leukemogenesis and the sensitivity to myeloid differentiation induced by ATRA.6 Clinicians soon noted that the ATRA-induced remission was accompanied by prompt improvement of the coagulopathy typical of this disease.10,11 Since then, a number of studies have confirmed that ATRA improves the hemostatic laboratory parameters and the bleeding complications. This article reviews the effects of ATRA on the coagulopathy of APL and the mechanisms by which this drug affects the hemostatic system. We also focus on how ATRA influences fatal hemorrhagic events during the induction of remission in APL.

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عنوان ژورنال:
  • Blood

دوره 91 9  شماره 

صفحات  -

تاریخ انتشار 1998