RESUMEN
OBJECTIVES: To compare the efficacy of venetoclax-azacitidine (VEN-AZA) with AZA in the real-life for patients with first relapsed or refractory acute myeloid leukaemia (R/R AML). METHODS: We retrospectively analysed R/R AML patients treated with VEN-AZA at the Institut Paoli Calmettes between September 2020 and February 2022. We compared them to a historical cohort of patients treated with AZA between 2010 and 2021. RESULTS: Thirty-five patients treated with VEN-AZA were compared with 140 patients treated with AZA. There were more favourable cytogenetics (25.7% vs. 8.6%; p = 0.01) and less FLT3-ITD mutated AML (8.8% vs. 25.5%; p = .049) in the VEN-AZA group. The overall 30-day mortality rate was 7.4% and the overall 90-day mortality was 20%, with no difference between the groups. The complete remission rate was 48.6% in the VEN-AZA group versus 15% (p < .0001). The composite complete response rate was 65.7% in the VEN-AZA group versus 23.6% (p < .0001). OS was 12.8 months in the VEN-AZA group versus 7.3 months (p = 0.059). Patients with primary refractory AML, poor-risk cytogenetics, prior hematopoietic stem-cell transplantation (HSCT) and FLT3-ITD mutated AML had lower response and survival rates. CONCLUSION: VEN-AZA was associated with a better response rate and a longer survival than AZA monotherapy in AML patients who relapsed after or were refractory to intensive chemotherapy.
Asunto(s)
Azacitidina , Compuestos Bicíclicos Heterocíclicos con Puentes , Leucemia Mieloide Aguda , Sulfonamidas , Humanos , Azacitidina/uso terapéutico , Terapia Recuperativa , Estudios Retrospectivos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
BACKGROUND: To address vaccine hesitancy and to build public trust, many factors need to be considered in the process of planning consistent public health interventions. After uncertain vaccinations of the Codroipo case, hesitant parents were surveyed about own beliefs and trusted sources of information. METHODS: A semi-structured phone survey was conducted between December 2017 and February 2018, collecting also age and educational level of respondents. RESULTS: The most trusted sources of information of the 258 surveyed parents were pediatricians (27.2%), general practitioners (25.4%) and institutional channels (12.1%). Highly educated parents trusted self-study of the scientific literature and expressed doubts about vaccine effectiveness more than others (p=0.0018). CONCLUSION: Despite the underlying improper vaccination issue undermined public trust, healthcare professionals and institutional channels maintained their role as trusted sources of information. Educational patterns emerged among doubtful parents should be considered by public health policies to effectively tackle vaccine hesitancy.
Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Padres , Humanos , Encuestas y Cuestionarios , Confianza , VacunaciónAsunto(s)
Leucemia Eritroblástica Aguda , Mutación , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia Eritroblástica Aguda/sangre , Leucemia Eritroblástica Aguda/clasificación , Leucemia Eritroblástica Aguda/genética , Leucemia Eritroblástica Aguda/mortalidad , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Organización Mundial de la SaludAsunto(s)
Biomarcadores de Tumor/genética , Aberraciones Cromosómicas , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Leucemia Eritroblástica Aguda/genética , Mutación/genética , Femenino , Humanos , Leucemia Eritroblástica Aguda/mortalidad , Leucemia Eritroblástica Aguda/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Tasa de SupervivenciaAsunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Análisis Mutacional de ADN , Leucemia Mielomonocítica Crónica/genética , Fosfoproteínas/genética , Adulto , Anciano , Anciano de 80 o más Años , Animales , Células de la Médula Ósea/citología , Estudios de Cohortes , Proteínas de Unión al ADN/genética , Regulación hacia Abajo , Exones , Femenino , Heterocigoto , Humanos , Masculino , Ratones , Persona de Mediana Edad , Mutación , Mutación Puntual , Estructura Terciaria de Proteína , Proteínas de Unión al ARN/genética , Transducción de SeñalAsunto(s)
Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Mutación/genética , Proteínas Nucleares/genética , Proteínas Represoras/genética , Adulto , Anciano , Anciano de 80 o más Años , Hibridación Genómica Comparativa , Femenino , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Nucleofosmina , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo Genético , Pronóstico , Adulto Joven , Tirosina Quinasa 3 Similar a fms/genética , Proteínas ras/genéticaRESUMEN
The t(8;16)(p11;p13) is a rare translocation involved in de novo and therapy-related myelomonocytic and monocytic acute leukemia. It fuses two genes encoding histone acetyltransferases (HATs), MYST3 located at 8p11 to CREBBP located at 16p13. Variant translocations involve other HAT-encoding genes such as EP300, MYST4, NCOA2 or NCOA3. MYST3-linked acute myeloid leukemias (AMLs) share specific clinical and biological features and a poor prognosis. Because of its rarity, the molecular biology of MYST3-linked AMLs remains poorly understood. We have established the genome and gene expression profiles of a multicentric series of 61 M4/M5 AMLs including 18 MYST3-linked AMLs by using array comparative genome hybridization (aCGH) (n=52) and DNA microarrays (n=44), respectively. We show that M4/5 AMLs have a variety of rare genomic alterations. One alteration, a gain of the MYB locus, was found recurrently and only in the MYST3-linked AMLs (7/18 vs 0/34). MYST3-AMLs have also a specific a gene expression profile, which includes overexpression of MYB, CD4 and HOXA genes. These features, reminiscent of T-cell acute lymphoid leukemia (ALL), suggest the targeting of a common T-myeloid progenitor.
Asunto(s)
Perfilación de la Expresión Génica/métodos , Genes myb/genética , Histona Acetiltransferasas/genética , Leucemia Mielomonocítica Aguda/genética , Antígenos CD4/genética , Hibridación Genómica Comparativa , Regulación Neoplásica de la Expresión Génica , Genoma Humano , Proteínas de Homeodominio/genética , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas Proto-Oncogénicas c-myb/genéticaAsunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Mutación Missense , Factores de Transcripción NFI/genética , Proteínas de Neoplasias/genética , Mutación Puntual , Policitemia Vera/genética , Eliminación de Secuencia , Sustitución de Aminoácidos , Secuencia de Bases , Cromosomas Humanos Par 1/genética , Errores Diagnósticos , Progresión de la Enfermedad , Femenino , Genes Supresores de Tumor , Humanos , Janus Quinasa 2/genética , Leucemia Monocítica Aguda/genética , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Factores de Transcripción NFI/química , Proteínas de Neoplasias/química , Policitemia Vera/diagnóstico , Estructura Terciaria de Proteína/genética , Trombocitemia Esencial/diagnósticoRESUMEN
Thirty cases of acute myeloid leukaemia (AML) with MYST histone acetyltransferase 3 (MYST3) rearrangement were collected in a retrospective study from 14 centres in France and Belgium. The mean age at diagnosis was 59.4 years and 67% of the patients were females. Most cases (77%) were secondary to solid cancer (57%), haematological malignancy (35%) or both (8%), and appeared 25 months after the primary disease. Clinically, cutaneous localization and disseminated intravascular coagulation were present in 30 and 40% of the cases, respectively. AMLs were myelomonocytic (7%) or monocytic (93%), with erythrophagocytosis (75%) and cytoplasmic vacuoles (75%). Immunophenotype showed no particularity compared with monocytic leukaemia without MYST3 abnormality. Twenty-eight cases carried t(8;16)(p11;p13) with MYST3-CREBBP fusion, one case carried a variant t(8;22)(p11;q13) and one case carried a t(8;19)(p11;q13). Type I (MYST3 exon 16-CREBBP exon 3) was the most frequent MYST3-CREBBP fusion transcript (65%). MYST3 rearrangement was associated with a poor prognosis, as 50% of patients deceased during the first 10 months. All those particular clinical, cytologic, cytogenetic, molecular and prognostic characteristics of AML with MYST3 rearrangement may have allowed an individualization into the World Health Organization classification.
Asunto(s)
Cromosomas Humanos Par 8 , Reordenamiento Génico , Histona Acetiltransferasas/genética , Leucemia Mieloide Aguda/genética , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Cartilla de ADN , Femenino , Humanos , Inmunofenotipificación , Hibridación Fluorescente in Situ , Cariotipificación , Leucemia Mieloide Aguda/inmunología , Masculino , Persona de Mediana Edad , Pronóstico , Reacción en Cadena de la Polimerasa de Transcriptasa InversaAsunto(s)
Cromosomas Humanos Par 12 , Cromosomas Humanos Par 5 , Coenzima A Ligasas/genética , Fusión de Oncogenes/genética , Policitemia Vera/genética , Proteínas Proto-Oncogénicas c-ets/genética , Proteínas Represoras/genética , Adulto , Anciano , Empalme Alternativo , Progresión de la Enfermedad , Resultado Fatal , Femenino , Humanos , Janus Quinasa 2 , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/genética , Masculino , Persona de Mediana Edad , Mutación , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Translocación Genética , Proteína ETS de Variante de Translocación 6Asunto(s)
Proteínas de Ciclo Celular/genética , Cromosomas Humanos Par 8 , Cromosomas Humanos Par 9 , Fusión Génica , Linfoma de Células T/genética , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Translocación Genética , Adulto , Autoantígenos , Humanos , Janus Quinasa 2 , Linfoma de Células T/enzimología , MasculinoAsunto(s)
Proteínas de Ciclo Celular/genética , Leucemia Eritroblástica Aguda/genética , Trastornos Mieloproliferativos/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Translocación Genética , Adulto , Autoantígenos , Niño , Cromosomas Humanos Par 8/genética , Cromosomas Humanos Par 9/genética , Femenino , Humanos , Janus Quinasa 2 , Masculino , Persona de Mediana EdadRESUMEN
Recurrent chromosome breakpoints in tumour cells may point to cancer genes, but not many have been molecularly characterised. We have used multicolour-banding fluorescence in situ hybridisation (mbanding-FISH) on breast tumour cell lines to identify regions of chromosome break created by inversions, duplications, insertions and translocations on chromosomes 1, 5, 8, 12 and 17. We delineate a total of 136 regions of break, some of them occurring with high frequency. We further describe two examples of dual-colour FISH characterisation of breakpoints, which target the 1p36 and 5p11-12 regions. Both breaks involve genes whose function is unknown to date. The mbanding-FISH strategy constitutes an efficient first step in the search for potential cancer genes.
