RESUMEN
Numerous prognostic markers were introduced to screen for patients with B-cell chronic lymphocytic leukemia (B-CLL) likely to have a progressive course, bearing the potential to facilitate risk-adapted treatment strategies. Extracellular adenosine triphosphate (ATP) functions as a "natural adjuvant" that boosts immune response in the tumor microenvironment. Ectonucleoside triphosphate diphosphohydrolase-1 (CD39/ENTPD1) is the ectonucleotidase that catalyzes the hydrolysis of ATP. The present study was conducted to analyze CD39 expression in T cells and B-CLL cells to evaluate its impact on the clinical course of patients with B-CLL and correlate its levels with well-established risk factors. T-cell CD39 expression was significantly increased in patients' peripheral blood compared to healthy controls. The higher levels were associated with advanced stages of disease and negatively interacted with time to first treatment. Overall, our data indicate that T-cell CD39 expression may identify subsets of patients with B-CLL with an unfavorable clinical outcome. Moreover, it can be incorporated into prognostic schema to improve the prediction of CLL disease progression.
Asunto(s)
Antígenos CD/metabolismo , Apirasa/metabolismo , Biomarcadores de Tumor , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/metabolismo , Anciano , Antígenos de Superficie/metabolismo , Linfocitos B/metabolismo , Linfocitos B/patología , Aberraciones Cromosómicas , Progresión de la Enfermedad , Femenino , Humanos , Inmunofenotipificación , Leucemia Linfocítica Crónica de Células B/mortalidad , Leucemia Linfocítica Crónica de Células B/terapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Linfocitos T/metabolismoRESUMEN
Clinical risk classification is inaccurate in predicting outcome in adult patients with acute lymphoblastic leukemia (ALL), sometimes resulting in patients receiving inappropriate chemotherapy or stem cell transplantation. To identify complementary markers suitable for further treatment stratification in patients with standard-risk (SR)/philadelphia-negative (Ph-negative) precursor B-ALL, we evaluated the predictive value of minimal residual disease (MRD) after induction and consolidation chemotherapy in strictly defined SR/Ph-negative precursor B-ALL patients who were treated with a standard protocol using quantitative real-time polymerase chain reaction with the rearranged immunoglobulin heavy chain gene as a molecular marker. The cytologic complete response (CR) rate was 92.3 % after induction. At this time point, the molecular CR rate was 73.9%. Patients with molecular CR (MolCR) after induction had a significantly higher probability of disease-free survival (DFS; 78.8 vs 30.8%; P = .001) and of overall survival (OS; 82.4 vs 41.7%; P < .0001) compared to patients with molecular failure (MolFail). MRD at end consolidation had the same significance. Quantitative MRD assessment identified patients with MolFail after induction and/or consolidation as a high-risk group, with 3-year DFS and OS rates of 28.6 and 35.7%, respectively. Patients with MolCR after induction and consolidation were classified as low-risk and had 3-year DFS rate of 89.7% and OS rate of 93.3%. Thus, MRD quantification during treatment identified prognostic subgroups within the otherwise homogeneous SR/Ph-negative precursor B-ALL population who may benefit from individualized treatment.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/diagnóstico , Neoplasia Residual/diagnóstico , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Adolescente , Adulto , Terapia Combinada , Quimioterapia de Consolidación , Femenino , Estudios de Seguimiento , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Masculino , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/mortalidad , Estadificación de Neoplasias , Neoplasia Residual/genética , Neoplasia Residual/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidad , Pronóstico , Estudios Prospectivos , ARN Mensajero/genética , Dosificación Radioterapéutica , Reacción en Cadena en Tiempo Real de la Polimerasa , Inducción de Remisión , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Riesgo , Tasa de Supervivencia , Adulto JovenRESUMEN
Th17 cells and their effector cytokines have emerged as important mediators in inflammatory and autoimmune diseases and serve as an ambitious field in current immunology research. Recent studies suggest a potential impact of Th17 cells on solid tumors but relatively little is known about their contribution in hematological malignancies. The current study was designed to investigate the possible involvement and clinical significance of circulating Th17 cells in acute leukemia. Flow cytometry was used to analyze percentages of Th17 cells in peripheral blood mononuclear cells from 93 acute leukemia patients (ALL, n = 30; AML, n = 63) and 40 healthy volunteers. Serum levels of IL-17 and IL-21 were measured using enzyme-linked immunosorbent assay. Circulating Th17 cells were increased in patients with acute leukemia (2.88 ± 0.65% and 2.90 ± 0.57% in ALL and AML patients, respectively) and were significantly higher than in healthy controls (1.10 ± 0.28%; P = 0.001). Furthermore, pretreatment Th17 cells were reduced significantly in patients who achieved complete remission after induction therapy (2.25 ± 0.44 % and 1.63 ± 0.27% in ALL and AML patients, respectively, P < 0.0001). Serum levels of IL-17 and IL-21 were significantly elevated in acute leukemia patients. Kaplan-Meier curves revealed a significantly longer overall survival in patients with high Th17 levels (P = 0.029 and P = 0.027 for ALL and AML, respectively). In the multivariate analysis, Th17 cells retained statistical significance for overall survival in patients with ALL (OR 0.331; P = 0.043) and AML (OR 0.489; P = 0.032). These results strongly suggest Th17 cells as a powerful new prognostic determinant which could serve as a potential therapeutic target to modulate anti-tumor response in acute leukemia patients.