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From the molecular model to the impact on prognosis: an overview on acute promyelocytic leukemia. Acute promyelocytic leukemia APL is a model of clinical applicability of the knowledge of molecular physiopathology. It is characterized by recurrent genetic involvement of the retinoic acid alpha receptor. The consequence is a protein with low sensibility to its ligand and a myeloid maturation arrest. Epidemiologically, it differs from other acute myeloid leukemia due to a higher incidence in young adults and in countries of "Latin" colonization. Differing from excellent results observed in developed countries, APL mortality in Brazil is still high, despite the wide availability of drugs.

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From the molecular model to the impact on prognosis: an overview on acute promyelocytic leukemia. Acute promyelocytic leukemia APL is a model of clinical applicability of the knowledge of molecular physiopathology. It is characterized by recurrent genetic involvement of the retinoic acid alpha receptor. The consequence is a protein with low sensibility to its ligand and a myeloid maturation arrest. Epidemiologically, it differs from other acute myeloid leukemia due to a higher incidence in young adults and in countries of "Latin" colonization.

Differing from excellent results observed in developed countries, APL mortality in Brazil is still high, despite the wide availability of drugs. Key words: Acute myeloid leukemia. Acute promyelocytic leukemia. Assim como nas outras LMAs, sintomas constitucionais como febre, astenia, hiporexia e perda ponderal predominam.

Medidas de controle da coagulopatia. High frequency of acute promyelocytic leukemia among Latinos with acute myeloid leukemia. The apparent excess of acute promyelocytic leukemia in infant acute leukemias in Brazil. Proposals for the classification of the acute leukaemias. Br J Haematol. Clinical characteristics, prognostic factors and multidrug-resistance related protein expression in 36 adult patients with acute promyelocytic leukemia. Eur J Haematol. Additional cytogenetic changes do not influence the outcome of patients with newly diagnosed acute promyelocytic leukemia treated with an ATRA plus anthracyclin based protocol.

Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Further evidence for a non-random chromosomal abnormality in acute promyelocytic leukemia. Int J Cancer. A previously uncharacterized gene, PML, is fused to the retinoic acid receptor alpha gene in acute promyelocytic leukaemia. Melnick A, Licht JD. Deconstructing a disease: RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia.

EMBO J. International Union of Pharmacology. Retinoic acid receptors. Pharmacol Rev. The acute promyelocytic leukemia-specific PML-RAR alpha fusion protein inhibits differentiation and promotes survival of myeloid precursor cells. Continuous treatment with all-trans retinoic acid causes a progressive reduction in plasma drug concentrations: implications for relapse and retinoid "resistance" in patients with acute promyelocytic leukemia.

Role of promyelocytic leukemia PML protein in tumor suppression. J Exp Med. PML is essential for multiple apoptotic pathways.

Nat Genet. Redner RL. Variations on a theme: the alternate translocations in APL. Altered myeloid development and acute leukemia in transgenic mice expressing PML-RAR alpha under control of cathepsin G regulatory sequences.

Inferior prognostic outcome in acute promyelocytic leukemia with alterations of FLT3 gene. Leuk Lymphoma. Douer D. The epidemiology of acute promyelocytic leukaemia. Best Pract Res Clin Haematol. Geographic differences in the incidence of cytogenetic abnormalities of acute myelogenous leukemia AML in Spain. Leuk Res. About the increased frequency of acute promyelocytic leukemia among Latinos: the experience from a center in Spain.

Acute promyelocytic leukemia: the study of t 15;17 translocation by fluorescent in situ hybridization, reverse transcriptase-polymerase chain reaction and cytogenetic techniques. Braz J Med Biol Res. PML-RARalpha fusion gene transcripts and biological features in acute promyelocytic leukemia patients.

Clin Lab Haematol. Early haemorrhagic morbidity and mortality during remission induction with or without all-trans retinoic acid in acute promyelocytic leukaemia. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med. Wintrobe's clinical hematology. Acute promyelocytic leukemia in 57 previously untreated patients. Acute promyelocytic leukemia: treatment results during a decade at Memorial Hospital.

All-trans retinoic acid upregulates thrombomodulin and downregulates tissue-factor expression in acute promyelocytic leukemia cells: distinct expression of thrombomodulin and tissue factor in human leukemic cells. Tissue factors on acute promyelocytic leukemia and endothelial cells are differently regulated by retinoic acid, arsenic trioxide and chemotherapeutic agents.

Potential role of interleukin-1 as the trigger for diffuse intravascular coagulation in acute nonlymphoblastic leukemia. Am J Med. A new procoagulant in acute leukemia. Platelet and fibrinogen survival in acute promyelocytic leukaemia. Br Med J;2 The specific activity of plasminogen activator inhibitor-1 in disseminated intravascular coagulation with acute promyelocytic leukemia.

The behavior of alpha2-plasmin inhibitor in fibrinolytic states. J Clin Invest. Reduced activity of TAFI thrombin-activatable fibrinolysis inhibitor in acute promyelocytic leukaemia. Annexin II and bleeding in acute promyelocytic leukemia. Evidence of fibrinogen breakdown by leukocyte enzymes in a patient with acute promyelocytic leukemia. Proteolysis of von Willebrand factor is decreased in acute promyelocytic leukaemia by treatment with all-trans-retinoic acid.

Acute myeloid leukemia with recurrent genetic abnormalities. Geneve: WHO; Immunofluorescent analysis with the anti-PML monoclonal antibody PG-M3 for rapid and accurate genetic diagnosis of acute promyelocytic leukemia. Ann Hematol. Cancer Chemother Pharmacol. Additional chromosomal abnormalities in patients with acute promyelocytic leukaemia APL do not confer poor prognosis: results of APL 93 trial.

All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. Clinical results. All-trans retinoic acid significantly reduces the incidence of early hemorrhagic death during induction therapy of acute promyelocytic leukemia.

A randomized comparison of all transretinoic acid ATRA followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia.

All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol. Retinoic acid syndrome: manifestations, pathogenesis, and treatment. Incidence, clinical features, and outcome of all trans-retinoic acid syndrome in cases of newly diagnosed acute promyelocytic leukemia. Clinico-biological features and outcome of acute promyelocytic leukemia patients with persistent polymerase chain reaction-detectable disease after the AIDA front-line induction and consolidation therapy.

Douer D, Tallman MS. Arsenic trioxide: new clinical experience with an old medication in hematologic malignancies. J Clin Oncol. Clinical features and outcomes of Brazilians with acute promyelocytic leukemia who received ATRA and anthracyclines. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. All the contents of this journal, except where otherwise noted, is licensed under a Creative Commons Attribution License.

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Acute promyelocytic leukemia

Acute promyelocytic leukemia was first characterized in [2] [3] by French and Norwegian physicians as a hyperacute fatal illness, [1] with a median survival time of less than a week. The symptoms tend to be similar to AML in general with the following being possible symptoms: [7]. Acute promyelocytic leukemia is characterized by a chromosomal translocation involving the retinoic acid receptor-alpha gene on chromosome 17 RARA. This fusion protein binds with enhanced affinity to sites on the cell's DNA, blocking transcription and differentiation of granulocytes. Although the chromosomal translocation involving RARA is believed to be the initiating event, additional mutations are required for the development of leukemia. Acute promyelocytic leukemia can be distinguished from other types of AML based on microscopic examination of the blood film or a bone marrow aspirate or biopsy as well as finding the characteristic rearrangement. The presence of promyelocytes containing multiple Auer rods termed faggot cells on the peripheral blood smear is highly suggestive of acute promyelocytic leukemia.

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This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly.

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