title: Prognostic factors in acute promyelocytic leukemia: strategies to define high-risk patients.
abstract: All trans retinoic acid (ATRA) has revolutionized the therapy of acute promyelocytic leukemia (APL). Treatment of this leukemia with ATRA in combination with chemotherapy has resulted in complete remission rates >90 % and long-term remission rates above 80 %. Furthermore, the combination of ATRA and arsenic trioxide (ATO) was shown to be safe and effective in frontline treatment and, for patients with low and intermediate risk disease, possibly superior to the standard ATRA and anthracycline-based regimen. However, in spite of this tremendous progress, APL still remains associated with a high incidence of early death due to the frequent occurrence of an abrupt bleeding diathesis. This hemorrhagic syndrome more frequently develops in high-risk APL patients, currently defined as those exhibiting >10 × 10(9)/L WBC at presentation. In addition to high WBC count, other molecular and immunophenotypic features have been associated with high-risk APL. Among them, the expression in APL blasts of the stem/progenitor cell antigen CD34, the neural adhesion molecule (CD56), and the T cell antigen CD2 help to identify a subset of patients at higher risk of relapse and often the expression of these markers is associated with high WBC count. At the molecular level, the short PML/RARA isoform and FLT3-internal tandem duplication (ITD) mutations have been associated with increased relapse risk. These observations indicate that extended immunophenotypic and molecular characterization of APL at diagnosis including evaluation of CD2, CD56, and CD34 antigens and of FLT3 mutations may help to better design risk-adapted treatment in this disease.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy. ugo.testa@iss.it.
authors.forename: Ugo
authors.initials: U
authors.lastname: Testa
authors.affiliation: Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy.|Laboratory of Neuro-Oncohematology, Santa Lucia Foundation, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo-Coco
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D014408:Biomarkers, Tumor; D002869:Chromosome Aberrations; D004268:DNA-Binding Proteins / Q000235:genetics; D004211:Disseminated Intravascular Coagulation / Q000209:etiology / Q000401:mortality; D006474:Hemorrhagic Disorders / Q000209:etiology / Q000401:mortality; D006801:Humans; D016130:Immunophenotyping; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D007958:Leukocyte Count; D009687:Nuclear Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000097:blood / Q000235:genetics; D010087:Oxides / Q000008:administration & dosage; D011379:Prognosis; D012307:Risk Factors; D020080:Tandem Repeat Sequences; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D001152:Arsenicals; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D010087:Oxides; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; D000077237:Arsenic Trioxide
keywords: Acute myeloid leukemia; Acute promyelocytic leukemia; Membrane markers; Prognosis