RESUMEN
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.
Asunto(s)
Regiones no Traducidas 3' , Biomarcadores de Tumor , Reordenamiento Génico , N-Metiltransferasa de Histona-Lisina/genética , Leucemia Mieloide Aguda/genética , Proteína de la Leucemia Mieloide-Linfoide/genética , ARN Mensajero , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Regulación Neoplásica de la Expresión Génica , Trasplante de Células Madre Hematopoyéticas , Humanos , Hibridación Fluorescente in Situ , Lactante , Estimación de Kaplan-Meier , Cariotipo , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Proteína del Locus del Complejo MDS1 y EV11/genética , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Pronóstico , Modelos de Riesgos Proporcionales , Translocación Genética , Trasplante Homólogo , Resultado del Tratamiento , Adulto Joven , Tirosina Quinasa 3 Similar a fms/genéticaAsunto(s)
Adalimumab/efectos adversos , Antiinflamatorios/efectos adversos , Médula Ósea/patología , Forma del Núcleo Celular/efectos de los fármacos , Enfermedad de Crohn/tratamiento farmacológico , Eosinofilia/patología , Eosinófilos/patología , Médula Ósea/efectos de los fármacos , Eosinofilia/inducido químicamente , Eosinófilos/efectos de los fármacos , Femenino , Humanos , Persona de Mediana Edad , PronósticoAsunto(s)
Anemia/patología , Médula Ósea/patología , Eritema Infeccioso/patología , Eritroblastos/ultraestructura , Mitosis , Complicaciones Posoperatorias/patología , Adulto , Anemia/etiología , Cromosomas Humanos/ultraestructura , Células Gigantes/ultraestructura , Humanos , Huésped Inmunocomprometido , Trasplante de Riñón , Masculino , Poliploidía , Complicaciones Posoperatorias/virologíaAsunto(s)
Leucemia Promielocítica Aguda/patología , Células Neoplásicas Circulantes/patología , Adulto , Dolor de Espalda , Resultado Fatal , Femenino , Células Precursoras de Granulocitos/patología , Humanos , Inmunofenotipificación , Leucemia de Mastocitos/diagnóstico , Leucemia de Mastocitos/patologíaRESUMEN
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.
Asunto(s)
Células de la Médula Ósea , Neoplasias de la Médula Ósea , Carcinoma Neuroendocrino , Eritrocitos , Neutrófilos , Fagocitosis , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/patología , Neoplasias de la Médula Ósea/metabolismo , Neoplasias de la Médula Ósea/patología , Carcinoma Neuroendocrino/metabolismo , Carcinoma Neuroendocrino/patología , Eritrocitos/metabolismo , Eritrocitos/patología , Femenino , Humanos , Persona de Mediana Edad , Neutrófilos/metabolismo , Neutrófilos/patologíaAsunto(s)
Variaciones en el Número de Copia de ADN , Granulocitos/patología , N-Metiltransferasa de Histona-Lisina/genética , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/genética , Proteína de la Leucemia Mieloide-Linfoide/genética , Adulto , Recuento de Células Sanguíneas , Médula Ósea/patología , Resultado Fatal , Femenino , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Síndromes Mielodisplásicos/tratamiento farmacológicoAsunto(s)
Sustitución de Aminoácidos , Trasplante de Células Madre Hematopoyéticas , Leucemia de Mastocitos/genética , Leucemia Mielomonocítica Crónica/genética , Mutación Missense , Proteínas de Neoplasias/genética , Neoplasias Primarias Secundarias/genética , Mutación Puntual , Proteínas Proto-Oncogénicas c-kit/genética , Aloinjertos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Progresión de la Enfermedad , Estudios de Asociación Genética , Humanos , Cadenas kappa de Inmunoglobulina/sangre , Leucemia de Mastocitos/tratamiento farmacológico , Leucemia de Mastocitos/patología , Leucemia de Mastocitos/terapia , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Leucemia Mielomonocítica Crónica/patología , Leucemia Mielomonocítica Crónica/terapia , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/sangre , Gammopatía Monoclonal de Relevancia Indeterminada/genética , Neoplasias Primarias Secundarias/tratamiento farmacológico , Neoplasias Primarias Secundarias/patología , Neoplasias Primarias Secundarias/terapia , Paraproteínas/análisis , Inducción de RemisiónRESUMEN
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.