RESUMEN
Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/ myeloproliferative neoplasm whose diagnosis is currently based on the elevation of peripheral blood monocytes to >1 × 10(9)/L, measured for ≥3 months. Diagnosis can be ambiguous; for example, with prefibrotic myelofibrosis or reactive monocytosis. We set up a multiparameter flow cytometry assay to distinguish CD14(+)/CD16(-) classical from CD14(+)/CD16(+) intermediate and CD14(low)/CD16(+) nonclassical monocyte subsets in peripheral blood mononucleated cells and in total blood samples. Compared with healthy donors and patients with reactive monocytosis or another hematologic malignancy, CMML patients demonstrate a characteristic increase in the fraction of CD14(+)/CD16(-) cells (cutoff value, 94.0%). The associated specificity and sensitivity values were 95.1% and 90.6% in the learning cohort (175 samples) and 94.1% and 91.9% in the validation cohort (307 samples), respectively. The accumulation of classical monocytes, which demonstrate a distinct gene expression pattern, is independent of the mutational background. Importantly, this increase disappears in patients who respond to hypomethylating agents. We conclude that an increase in the fraction of classical monocytes to >94.0% of total monocytes is a highly sensitive and specific diagnostic marker that rapidly and accurately distinguishes CMML from confounding diagnoses.
Asunto(s)
Citometría de Flujo/métodos , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Receptores de Lipopolisacáridos/sangre , Monocitos , Receptores de IgG/sangre , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Monocitos/patología , Sensibilidad y EspecificidadAsunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Azacitidina/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Síndromes Mielodisplásicos/tratamiento farmacológico , Cariotipo Anormal , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Azacitidina/administración & dosificación , Azacitidina/efectos adversos , Enfermedades de la Médula Ósea/inducido químicamente , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Neutropenia Febril/inducido químicamente , Femenino , Francia/epidemiología , Hospitalización/estadística & datos numéricos , Humanos , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidad , Masculino , Estudios Multicéntricos como Asunto , Síndromes Mielodisplásicos/mortalidad , Insuficiencia Renal Crónica/epidemiología , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Leucemia Mieloide Aguda/etiología , Linfoma , Síndromes Mielodisplásicos/etiología , Neoplasias Primarias Secundarias , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidad , Linfoma/mortalidad , Linfoma/terapia , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/mortalidad , Evaluación del Resultado de la Atención al Paciente , Radioterapia/efectos adversos , Radioterapia/métodosRESUMEN
Azacitidine (AZA), the reference treatment for most higher-risk myelodysplastic (MDS) patients can also improve overall survival (OS) in elderly acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy, but reliable biological markers predicting response and OS in patients treated with AZA are lacking. In a preliminary study, we found that an increase of the percentage of BCL2L10, an anti-apoptotic member of the bcl-2 family, was correlated with AZA resistance. In this study, we assessed prospectively by flow cytometry the prognostic value of BCL2L10 positive bone marrow mononuclear cells in 70 patients (42 MDS and 28 AML), prior to AZA treatment.In patients with baseline marrow blasts below 30%, the baseline percentage of bone marrow BCL2L10 positive cells inversely correlated with response to AZA and OS independently of the International Prognostic Scoring System (IPSS) and IPSS-revised (IPSS-R). Specifically, OS was significantly lower in patients with more than 10% BCL2L10 positive cells (median 8.3 vs 22.9 months in patients with less than 10% positivity, p = 0,001). In summary, marrow BCL2L10 positive cells may be a biomarker for azacitidine response and OS, with a potential impact in clinical practice.