RESUMO
OBJECTIVE: MLL gene is involved in more than 80 known genetic fusions in acute leukemia. To study the relevance of MLL partner gene and selected gene's expression, in this work, we have studied a cohort of 20 MLL-rearranged acute myeloid leukemia (AML). METHODS: Twenty MLL-rearranged AML patients along with a control cohort of 138 AML patients are included in this work. By RT-PCR and sequencing, MLL genetic fusion was characterized, and relative gene expression quantification was carried out for EVI1, MEIS1, MLL-3', RUNX1, SETBP1, HOXA5, and FLT3 genes. Risk stratification and association of MLL genetic partner and gene expression to overall survival, in the context of received therapy, were performed. RESULTS: MLLr cohort showed to have an OS more similar to intermediate-risk AML. Type of MLL genetic partner showed to be relevant in allo-HSCT response; having MLLT1 and MLLT3, a better benefit from it. Expression of MLL-3' region, EVI1 and FLT3, showed association with OS in patients undergoing allo-HSCT. CONCLUSION: We show that the MLL genetic partner could have implications in allo-HSCT response, and we propose three genes whose expression could be useful for the prognosis of this leukemia in patients undergoing allo-HSCT: 3' region of MLL, EVI1, and FLT3.
Assuntos
Regiões 3' não Traduzidas , Biomarcadores Tumorais , Rearranjo Gênico , Histona-Lisina N-Metiltransferase/genética , Leucemia Mieloide Aguda/genética , Proteína de Leucina Linfoide-Mieloide/genética , RNA Mensageiro , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Regulação Neoplásica da Expressão Gênica , Transplante de Células-Tronco Hematopoéticas , Humanos , Hibridização in Situ Fluorescente , Lactente , Estimativa de Kaplan-Meier , Cariótipo , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Proteína do Locus do Complexo MDS1 e EVI1/genética , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Prognóstico , Modelos de Riscos Proporcionais , Translocação Genética , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem , Tirosina Quinase 3 Semelhante a fms/genéticaAssuntos
Adalimumab/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Medula Óssea/patologia , Forma do Núcleo Celular/efeitos dos fármacos , Doença de Crohn/tratamento farmacológico , Eosinofilia/patologia , Eosinófilos/patologia , Medula Óssea/efeitos dos fármacos , Eosinofilia/induzido quimicamente , Eosinófilos/efeitos dos fármacos , Feminino , Humanos , Pessoa de Meia-Idade , PrognósticoAssuntos
Anemia/patologia , Medula Óssea/patologia , Eritema Infeccioso/patologia , Eritroblastos/ultraestrutura , Mitose , Complicações Pós-Operatórias/patologia , Adulto , Anemia/etiologia , Cromossomos Humanos/ultraestrutura , Células Gigantes/ultraestrutura , Humanos , Hospedeiro Imunocomprometido , Transplante de Rim , Masculino , Poliploidia , Complicações Pós-Operatórias/virologiaRESUMO
Eosinophils in peripheral blood account for 0.3-5% of leukocytes, which is equivalent to 0.05-0.5 × 109/L. A count above 0.5 × 109/L is considered to indicate eosinophilia, while a count equal to or above 1.5 × 109/L is defined as hypereosinophilia. In bone marrow aspirate, eosinophilia is considered when eosinophils make up more than 6% of the total nuclear cells. In daily clinical practice, the most common causes of reactive eosinophilia are non-hematologic, whether they are non-neoplastic (allergic diseases, drugs, infections, or immunological diseases) or neoplastic (solid tumors). Eosinophilia that is associated with a hematological malignancy may be reactive or secondary to the production of eosinophilopoietic cytokines, and this is mainly seen in lymphoid neoplasms (Hodgkin lymphoma, mature T-cell neoplasms, lymphocytic variant of hypereosinophilic syndrome, and B-acute lymphoblastic leukemia/lymphoma). Eosinophilia that is associated with a hematological malignancy may also be neoplastic or primary, derived from the malignant clone, usually in myeloid neoplasms or with its origin in stem cells (myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions, acute myeloid leukemia with core binding factor translocations, mastocytosis, myeloproliferative neoplasms, myelodysplastic/myeloproliferative neoplasms, and myelodysplastic neoplasms). There are no concrete data in standardized cytological and cytometric procedures that could predict whether eosinophilia is reactive or clonal. The verification is usually indirect, based on the categorization of the accompanying hematologic malignancy. This review focuses on the broad differential diagnosis of hematological malignancies with eosinophilia.
Assuntos
Células da Medula Óssea , Neoplasias da Medula Óssea , Carcinoma Neuroendócrino , Eritrócitos , Neutrófilos , Fagocitose , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Neoplasias da Medula Óssea/metabolismo , Neoplasias da Medula Óssea/patologia , Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/patologia , Eritrócitos/metabolismo , Eritrócitos/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Neutrófilos/patologiaAssuntos
Variações do Número de Cópias de DNA , Granulócitos/patologia , Histona-Lisina N-Metiltransferase/genética , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Proteína de Leucina Linfoide-Mieloide/genética , Adulto , Contagem de Células Sanguíneas , Medula Óssea/patologia , Evolução Fatal , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Síndromes Mielodisplásicas/tratamento farmacológicoAssuntos
Substituição de Aminoácidos , Transplante de Células-Tronco Hematopoéticas , Leucemia de Mastócitos/genética , Leucemia Mielomonocítica Crônica/genética , Mutação de Sentido Incorreto , Proteínas de Neoplasias/genética , Segunda Neoplasia Primária/genética , Mutação Puntual , Proteínas Proto-Oncogênicas c-kit/genética , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Progressão da Doença , Estudos de Associação Genética , Humanos , Cadeias kappa de Imunoglobulina/sangue , Leucemia de Mastócitos/tratamento farmacológico , Leucemia de Mastócitos/patologia , Leucemia de Mastócitos/terapia , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Leucemia Mielomonocítica Crônica/patologia , Leucemia Mielomonocítica Crônica/terapia , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/genética , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/terapia , Paraproteínas/análise , Indução de RemissãoRESUMO
Allogeneic hematopoietic stem cell transplantation (HSCT) represents the best therapeutic option for many patients with acute myeloid leukemia (AML). However, relapse remains the main cause of mortality after transplantation. The detection of measurable residual disease (MRD) by multiparameter flow cytometry (MFC) in AML, before and after HSCT, has been described as a powerful predictor of outcome. Nevertheless, multicenter and standardized studies are lacking. A retrospective analysis was performed, including 295 AML patients undergoing HSCT in 4 centers that worked according to recommendations from the Euroflow consortium. Among patients in complete remission (CR), MRD levels prior to transplantation significantly influenced outcomes, with overall (OS) and leukemia free survival (LFS) at 2 years of 76.7% and 67.6% for MRD-negative patients, 68.5% and 49.7% for MRD-low patients (MRD < 0.1), and 50.5% and 36.6% for MRD-high patients (MRD ≥ 0.1) (p < 0.001), respectively. MRD level did influence the outcome, irrespective of the conditioning regimen. In our patient cohort, positive MRD on day +100 after transplantation was associated with an extremely poor prognosis, with a cumulative incidence of relapse of 93.3%. In conclusion, our multicenter study confirms the prognostic value of MRD performed in accordance with standardized recommendations.