RESUMEN
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mielomonocítica Crónica , Humanos , Pronóstico , Trasplante Homólogo/efectos adversos , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/etiologíaRESUMEN
Transplantation-associated thrombotic microangiopathy (TA-TMA) is one of the serious complications mostly occurring within 100 days after hematopoietic stem cell transplantation (HSCT). Risk factors of TA-TMA include genetic predispositions, GVHD, and infections. The pathophysiological mechanisms of TA-TMA start with endothelial injury caused by complement activation, which leads to microvascular thrombosis, and microvascular hemolysis, ultimately resulting in multi-organ dysfunction. In recent years, the development of complement inhibitors has markedly improved the prognosis of TA-TMA patients. This review will give an update on risk factors, clinical manifestations, diagnosis, and treatment of TA-TMA, so as to provide references for clinical practice.
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Trasplante de Células Madre Hematopoyéticas , Trombosis , Microangiopatías Trombóticas , Humanos , Microangiopatías Trombóticas/diagnóstico , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/terapia , Pronóstico , Trombosis/etiología , Factores de Riesgo , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
In recent decades, haploidentical stem cell transplantation (haplo-SCT) to treat severe aplastic anemia (SAA) has achieved remarkable progress. However, long-term results are still lacking. We conducted a multicenter prospective study involving SAA patients who underwent haplo-SCT as salvage therapy. Long-term outcomes were assessed, mainly focusing on survival and quality of life (QoL). Longitudinal QoL was prospectively evaluated during pretransplantation and at 3 and 5 years posttransplantation using the SF-36 scale in adults and the PedsQL 4.0 scale in children. A total of 287 SAA patients were enrolled, and the median follow-up was 4.56 years (range, 3.01-9.05 years) among surviving patients. During the long-term follow-up, 268 of 275 evaluable patients (97.5%) obtained sustained full donor chimerism, and 93.4% had complete hematopoietic recovery. The estimated overall survival and failure-free survival for the whole cohort at 9 years were 85.4% ± 2.1% and 84.0% ± 2.2%, respectively. Age (≥18 years) and a poorer performance status (ECOG >1) were identified as risk factors for survival outcomes. For QoL recovery after haplo-SCT, we found that QoL progressively improved from pretransplantation to the 3-year and 5-year time points with statistical significance. The occurrence of chronic graft versus host disease was a risk factor predicting poorer QoL scores in both the child and adult cohorts. At the last follow-up, 74.0% of children and 72.9% of adults returned to normal school or work. These inspiring long-term outcomes suggest that salvage transplantation with haploidentical donors can be routine practice for SAA patients without human leukocyte antigen (HLA)-matched donors.
Asunto(s)
Anemia Aplásica , Enfermedad Injerto contra Huésped , Niño , Adulto , Humanos , Adolescente , Trasplante Haploidéntico/métodos , Estudios de Seguimiento , Estudios Prospectivos , Calidad de Vida , Anemia Aplásica/terapia , Enfermedad Injerto contra Huésped/etiologíaRESUMEN
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a curative option for severe aplastic anemia (SAA), and transplantation from identical sibling donors (ISD) has been recommended as a first-line treatment. Haploidentical donor (HID) transplantation for SAA has made great advances; thus, an increased role of HID-SCT in SAA should be considered. We performed a national registry-based analysis comparing long-term outcomes in the upfront HID or upfront ISD SCT setting. A total of 342 SAA patients were enrolled, with 183 patients receiving HID SCT and 159 receiving ISD SCT. The estimated 9-year overall survival and failure-free survival were 87.1±2.5% and 89.3±3.7% (P=0.173) and 86.5±2.6% versus 88.1±3.8% (P=0.257) for patients in the HID and ISD SCT groups, respectively. Transplantation from HID or ISD SCT has greatly improved quality of life (QoL) levels post-HSCT compared to pre-HSCT. The occurrence of chronic graft-versus-host disease was the only identified adverse factor affecting each subscale of QoL. Physical and mental component summaries in adults as well as physical, mental, social, and role well-being in children were all similar between HID and ISD SCT at 5-year time points. At the last follow-up, the proportion of returning to society was comparable between the HID and ISD groups, showing 78.0% versus 84.6% among children and 74.6% versus 81.2% among adults. These data suggest that haploidentical transplant can be considered a potential therapeutic option in the upfront setting for SAA patients in the absence of an HLA-identical related or unrelated donor.
Asunto(s)
Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adulto , Niño , Humanos , Anemia Aplásica/terapia , Hermanos , Calidad de Vida , Enfermedad Injerto contra Huésped/etiología , Donante no Emparentado , Sistema de Registros , Acondicionamiento PretrasplanteRESUMEN
Checkpoint kinase 1 inhibitors (CHK1i) have shown impressive single-agent efficacy in treatment of certain tumors, as monotherapy or potentiators of chemotherapy in clinical trials, but the sensitive tumor types and downstream effectors to dictate the therapeutic responses to CHK1i remains unclear. In this study we first analyzed GDSC (Genomics of Drug Sensitivity in Cancer) and DepMap database and disclosed that hematologic malignancies (HMs) were relatively sensitive to CHK1i or CHK1 knockdown. This notion was confirmed by examining PY34, a new and potent in-house selective CHK1i, which exhibited potent anti-HM effect in vitro and in vivo, as single agent. We demonstrated that the downregulation of c-Myc and its signaling pathway was the common transcriptomic profiling response of sensitive HM cell lines to PY34, whereas overexpressing c-Myc could partially rescue the anticancer effect of PY34. Strikingly, we revealed the significant correlations between downregulation of c-Myc and cell sensitivity to PY34 in 17 HM cell lines and 39 patient-derived cell (PDC) samples. Thus, our results demonstrate that HMs are more sensitive to CHK1i than solid tumors, and c-Myc downregulation could represent the CHK1i efficacy in HMs.
Asunto(s)
Proteínas de Unión al ADN/antagonistas & inhibidores , Regulación hacia Abajo/efectos de los fármacos , Neoplasias Hematológicas/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Factores de Transcripción/antagonistas & inhibidores , Animales , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/antagonistas & inhibidores , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/deficiencia , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patología , Humanos , Ratones , Ratones Endogámicos NOD , Ratones Desnudos , Ratones SCID , Estructura Molecular , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Inhibidores de Proteínas Quinasas/química , Relación Estructura-Actividad , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
OBJECTIVE: To study the potential significance and clinical application of FGFR1 gene abnormality in the diagnosis, clinical features, pathological mechanism and treatment in hematological tumors. METHODS: Clinical data of total of 29 patient with chromosome of 8 short arm (8P) abnormality who had more comprehensive medical history from 2013 to 2018 were collected. The karyotype analysis of bone marrow chromosomes in patients was carried out by using chromosome R band banding technique. FGFR1 gene was detected by using fluorescence in situ hybridization (FISH). RESULTS: Seven cases of FGFR1 gene abnormalities were decteted, including 3 cases of FGFR1 gene amplification, 2 cases of translocation, and 2 cases of deletion. Five patients with FGFR1 gene amplification or deletion not accompaned with eosinophilia, moreover the chromosome was a complex karyotype with poor prognosis; Two cases of FGFR1 gene translocation were non-complex chromosomal translocation and one of which survived for 6 years after bone marrow transplantation, the other chromosome karyotype showed no rearrangement of 8 short arm. However, FGFR1 gene rearrangement was confirmed by FISH analysis, which was a rare insertional translocation. CONCLUSION: FGFR1 gene amplification or deletion often occur in cases with complex karyotype, which not accompany eosinophilia, moreover have poor prognosis. The patients with FGFR1 gene translocation accompany eosinophilia which is consistent with the clinical characteristics of myeloid / lymphoid neoplasms with FGFR1 abnormality. Karyotype analysis combined with FISH method can improve the detection of abnormal clones.
Asunto(s)
Neoplasias Hematológicas/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Aberraciones Cromosómicas , Neoplasias Hematológicas/metabolismo , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Translocación GenéticaRESUMEN
RATIONALE: Paradoxical embolism (PE) is an important cause of cryptogenic stroke, particularly in young patients, which usually have a relation with an unexpected route in circulation. Here we report a rare case of cryptogenic stroke carried 2 uncommon malformations. PATIENT CONCERNS: A 48-year-old female experienced double neurological events in just 2 months. DIAGNOSIS: Patent foramen ovale was diagnosed with transesophageal echocardiography and successfully occluded in the first admission due to stroke. In the second admission, chest tomographic angiography found a chordae shadow in the right middle lobe, was the first clue for pulmonary arteriovenous fistula (PAVF), thereafter further confirmed by the enhanced pulmonary computed tomographic angiography. INTERVENTIONS: This patient then received intervention occlusion therapy with coils for PAVF under the help of microcatheter. Given the possible native origin of the thrombus in PAVF due to the spiral morphology, dual antiplatelet therapy was prescribed for this patient for the first 3 months to prevent device-related embolism after discharge, and the following single antiplatelet therapy was mandated. OUTCOMES: No recanalization was detected on the follow-up enhanced pulmonary computed tomographic angiography (PCTA), no neurological defect event recurred in the 16 months of follow-up. LESSONS: Computed tomograph (CT) deserved more value in screening and depicting the morphology of the PAVF, particular in young adults with no apparent arteriosclerotic risk factor. Microcatheter would be helpful for intervention treatment. Antiplatelet therapy might be adequate in specific patients, yet definitely need more evidence to verify.
Asunto(s)
Fístula Arteriovenosa/complicaciones , Embolia Paradójica/etiología , Foramen Oval Permeable/complicaciones , Arteria Pulmonar/anomalías , Venas Pulmonares/anomalías , Accidente Cerebrovascular/etiología , Fístula Arteriovenosa/diagnóstico por imagen , Fístula Arteriovenosa/terapia , Angiografía por Tomografía Computarizada , Femenino , Foramen Oval Permeable/terapia , Humanos , Persona de Mediana Edad , Accidente Cerebrovascular/diagnóstico por imagenRESUMEN
FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) is one of the most common somatic mutations in acute myeloid leukemia (AML). However, the molecular structure characteristics and widely accepted prognostic factors for FLT3-ITD are still not well described. This study aimed to retrospectively examine 81 patients with FLT3-ITD-positive AML diagnosed and treated at the First Affiliated Hospital of Zhejiang University from December 2013 to March 2018 using the next-generation sequencing 185-gene platform. High variant allele frequency (VAF) [> 0.48, P = 0.0089 for overall survival (OS), P = 0.13 for relapse-free survival (RFS)], multiple ITDs (> 1 ITDs, P = 0.011 for OS, P = 0.033 for RFS) and longer insertion length (> 69 bp, P = 0.14 for OS, P = 0.0078 for RFS) predicted poor survival. The study further proposed an easily applicable scoring model for OS using the Least Absolute Shrinkage and Selector Operation (LASSO) Cox regression model. Also, an independent cohort of 30 patients was used for external model validation. The mode was expressed as follows: 0.659 × FLT3-ITD VAF + 0.375 × FLT3-ITD number + 0.807 × Age + 0.688 × DNMT3A + 1.939 × U2AF1 (FLT3-ITD VAF > 0.48 scored 1; FLT3-ITD number scored 1 if carried 1 ITD, 2 if carried ≥ 2 ITDs; age > 44 years scored 1, the presence of DNMT3A or U2AF1 scored 1; 0 for other conditions). It categorized patients into low-risk (L-R, score < 1, n = 20) and high-risk (H-R, score ≥ 1, n = 61) groups based on the risk score with a significant difference in survival (3-year OS, P < 0.0001; 3-year RFS, P = 0.0005). A prognostic nomogram that integrated these five factors was developed with a concordance index calculation [OS: 0.68, 95% CI (0.64-0.72)].
RESUMEN
A Gram-stain-negative, rod-shaped and facultatively anaerobic strain, designated CG51T, was isolated from marine sediment collected from a coastal area in Weihai, PR China. Strain CG51T grew at 4-37 °C (optimum, 28-30 °C), with 1.0-6.0â% (w/v) NaCl (2.0-3.0â%) and at pH 6.0-8.5 (pH 7.0-7.5). The predominant fatty acids were iso-C15â:â0, anteiso-C15â:â0 and iso-C14â:â0. Major polar lipids included an unidentified lipid and a phospholipid. The respiratory quinone was MK-7 and the genomic DNA G+C content was 35.9 mol%. The results of phylogenetic analysis based on 16S rRNA gene sequences placed strain CG51T in the genus Labilibacter with the close relatives being Labilibacter marinus Y11T and Labilibacter aurantiacus HQYD1T, exhibiting 96.5 and 96.3â% 16S rRNA pairwise similarity, values which are clearly below the 98.7â% threshold value recommended for species demarcation. Based on the phylogenetic, physiological, chemotaxonomic and genetic data, strain CG51T represents a novel species within the genus Labilibacter, for which the name Labilibacter sediminis sp. nov. is proposed. The type strain is CG51T (=MCCC 1K03739T=JCM 33138T).
Asunto(s)
Bacteroidetes/clasificación , Sedimentos Geológicos/microbiología , Filogenia , Agua de Mar/microbiología , Técnicas de Tipificación Bacteriana , Bacteroidetes/aislamiento & purificación , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
To compare the efficacy and toxicity of a novel regimen called FBA, consisting of fludarabine, busulfan, and cytarabine, with the standard BuCy2 regimen for younger adult patients with acute myeloid leukemia, we conducted a prospective randomized phase II study. Patients in complete remission were randomly assigned to receive either the FBA (n = 56) or the BuCy2 regimen (n = 55). The difference in 100-day transplant-related mortality (TRM) was not statistically significant between the two arms (1.79% for FBA versus 5.45% for BuCy2, P = 0.260), as were the cumulative incidences of relapse, TRM, overall survival (OS) and event-free survival (EFS) at 3 years. However, the 100-day cumulative incidences of grades II-IV and III-IV acute graft-versus-host disease (aGVHD) were lower in the FBA group [(8.93% versus 21.86%, P = 0.032) (1.79% versus 9.09%, P = 0.025)]. The 3-year GVHD and relapse-free survival (GRFS) was 31.20% for the FBA group and 14.96% for the BuCy2 group (P = 0.004). The incidences of diarrhea and severe oral mucositis within the first 30 days post-transplantation were lower in the FBA group [(28.57% versus 65.45%; P < 0.001) (51.79% versus 70.91%; P = 0.039)]. In conclusion, allogenic transplantation with the FBA regimen achieved similar TRM, relapse rate, OS and EFS, as that with the BuCy2 regimen but with less frequent and less severe complications in early stage after transplantation and a trend toward higher GRFS.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Busulfano/uso terapéutico , Citarabina/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Vidarabina/análogos & derivados , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Busulfano/farmacología , Ciclofosfamida/farmacología , Ciclofosfamida/uso terapéutico , Citarabina/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Vidarabina/farmacología , Vidarabina/uso terapéutico , Adulto JovenRESUMEN
RATIONALE: Diffuse large B-cell lymphoma (DLBCL) is a neoplasm of large B lymphoid cells that exhibits diffuse growth patterns. Patients may present with nodal and/or extranodal disease. The most common extranodal site is the gastrointestinal tract, while skin is less common. PATIENT CONCERNS: We report a case of secondary skin involvement of an original gastric DLBCL, which has achieved a complete response after treatment with chidamide. DIAGNOSES: Initially, the diagnosis of gastric DLBCL is clear, and this patient responded well to systemic chemotherapy (rituximab + cyclophosphamide + epirubicin + vincristine + prednisone) after 8 cycles. Thirty months later, some rapidly enlarging skin nodules on his arm were found. These skin nodules were diagnosed as secondary cutaneous DLBCL based on the clinical features, positron emission tomography-computed tomography, and histomorphologic and immunohistochemical expression. INTERVENTIONS: Steroids, interferon-α, and radiation had little therapeutic effect. We treated the patient with chidamide at 30âmg twice per week in combination with dexamethasone. OUTCOMES: The skin nodules regressed 3 weeks later. During the 1-year follow-up period, the patient is still in treatment with chidamide without adverse reactions. LESSONS: To the best of our knowledge, this is the first case of secondary skin DLBCL reported to exhibit a complete response to chidamide, which provides a novel therapeutic strategy for secondary skin DLBCL. However, more cases are still needed to further validate its efficacy.
Asunto(s)
Aminopiridinas/uso terapéutico , Antineoplásicos/uso terapéutico , Benzamidas/uso terapéutico , Linfoma de Células B Grandes Difuso/patología , Linfoma no Hodgkin/patología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/secundario , Neoplasias Gástricas/patología , Diagnóstico Diferencial , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Neoplasias Cutáneas/diagnóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
BACKGROUND: It remains unknown whether Non-POU-domain-containing octamer-binding protein (NonO) plays a causative role in plaque destabilization. We hypothesized that NonO gene silencing may stabilize atherosclerotic plaque by increasing P4Hα1 expression and inhibiting the inflammation. METHODS AND RESULTS: Vulnerable atherosclerotic plaques were induced in ApoE-/- mice by high fat diet, perivascular collar placement and mental stress. Compared with normal carotid arteries, those contained vulnerable plaques had high NonO expression. In another in vivo experiment, mice contained vulnerable plaques were randomly divided into 5 groups to receive physiological saline, si-N.C-lentivirus (LV), si-NonO-LV, pGC-GFP-LV and NonO-LV, respectively. NonO overexpression increased while NonO silencing decreased the incidence of carotid plaque disruption. NonO overexpression enhanced macrophage infiltration and lipid deposition but reduced the content of vascular smooth muscle cells and collagen in plaques, leading to an increased plaque vulnerability index, whereas NonO silencing exhibited the opposite effect. In addition, NonO overexpression increased the expression of proinflammatory cytokines and matrix metalloproteinases and decreased the expression of P4Hα1 both in vivo and in vitro, whereas NonO silencing showed the contrary effect. NonO co-immunoprecipitated with NF-κB p65, and promoted its nuclear translocation and phosphorylation, and these effects were reversed by NonO silencing. CONCLUSION: NonO may promote plaque destabilization and increase the incidence of plaque disruption in ApoE-/- mice by inducing the expression of inflammatory cytokines and matrix metalloproteinases and suppressing that of P4Hα1. The mechanism may involve the interaction of NonO with NF-κB leading to enhanced NF-κB nuclear translocation and phosphorylation.
Asunto(s)
Apolipoproteínas E/deficiencia , Proteínas de Unión al ADN/biosíntesis , Silenciador del Gen/fisiología , FN-kappa B/metabolismo , Placa Aterosclerótica/metabolismo , Transducción de Señal/fisiología , Animales , Apolipoproteínas E/genética , Citocinas/biosíntesis , Citocinas/genética , Proteínas de Unión al ADN/antagonistas & inhibidores , Proteínas de Unión al ADN/genética , Masculino , Ratones , Ratones Noqueados , FN-kappa B/genética , Placa Aterosclerótica/genética , Placa Aterosclerótica/patología , Células RAW 264.7 , Proteínas de Unión al ARNAsunto(s)
Absceso Abdominal/etiología , Adenocarcinoma/patología , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/efectos adversos , Neoplasias Pancreáticas/patología , Gastropatías/etiología , Absceso Abdominal/terapia , Adenocarcinoma/diagnóstico , Drenaje , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/diagnóstico , Gastropatías/terapiaRESUMEN
Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are common types of acute leukemia in adults and cause low survival rate and poor outcome after 5 years despite high rates of complete remission (CR) with modern chemotherapeutic regimens. To understand the distinct mechanisms in leukemogenesis for ALL and AML and to identify markers for diagnosis and treatment, lncRNA and mRNA expression profiles of AML and ALL patients and healthy controls were generated using microarray analysis. For comparison, the differentially expressed mRNA functions were annotated using gene ontology (GO) and pathway analysis. The microarray revealed that 1011 lncRNAs and 2656 mRNAs differed in AML patients and 6069 lncRNAs and 5338 mRNAs differed in ALL patients from those in healthy controls. The GO terms and KEGG pathway annotation data revealed that the olfactory receptor activity, G-protein coupled receptor activity and olfactory transduction-related genes were significantly associated with AML and ALL. Co-expression network analysis indicated that 108 lncRNAs and 85 mRNAs were included in the co-expression network. This study is the first to explore genome-wide lncRNA expression and co-expression with mRNA patterns in AML and ALL using microarray technology and could provide basic information for new biomarkers or treatment targets to alleviate AML and ALL.
Asunto(s)
Leucemia Mieloide Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , ARN Mensajero/metabolismo , ARN no Traducido/metabolismo , Enfermedad Aguda , Adulto , Perfilación de la Expresión Génica , Ontología de Genes , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/genética , ARN no Traducido/genética , Transducción de Señal/genéticaRESUMEN
BACKGROUND: Granulomatous mastitis (GM) is a chronic inflammatory breast lesion. Its etiology remains incompletely defined. Although mounting evidence suggests the involvement of Corynebacterium in GM, there has been no systematic study of GM bacteriology using -omics technology. METHODS: The bacterial diversity and relative abundances in breast abscesses from 19 women with GM were investigated using 16S rDNA metagenomic sequencing and Sanger sequencing. A quantitative PCR (qPCR) assay was also developed to identify Corynebacterium kroppenstedtii. RESULTS: A bioinformatic analysis revealed that Corynebacterium was present in the 19 GM patients, with abundances ranging from 1.1% to 58.9%. Of note, Corynebacterium was the most abundant taxon in seven patients (more than a third of the subjects). The predominance of Corynebacterium kroppenstedtii infection (11 of 19 patients, 57.9%) was confirmed with Sanger sequencing and the qPCR assay. CONCLUSIONS: This study profiled the microbiota of patients with GM and indicated an important role for Corynebacterium, and in particular C. kroppenstedtii, in the pathogenesis of this disease.
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Absceso/microbiología , Mama/microbiología , Infecciones por Corynebacterium/microbiología , Corynebacterium/aislamiento & purificación , Mastitis Granulomatosa/microbiología , Metagenómica , Microbiota , Adulto , Corynebacterium/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Femenino , Humanos , Análisis de Secuencia de ADNRESUMEN
Myeloid tumor possessing platelet-derived growth factor receptor ß (PDGFRß) gene rearrangement is a rare hematological malignancy, which presents with typical characteristics of myeloid proliferation disorders and eosinophilia. In the present study, an elderly chronic myelomonocytic leukemia patient was diagnosed with chromosome rearrangement. Fluorescence in situ hybridization (FISH) was conducted with a PDGFRß isolate probe, and gene translocation between PDGFRß on chromosome 5 and genes on the chromosomes of group D (13-15) was detected. Karyotype analysis revealed a chromosome 5 break, and PDGFRß-thyroid hormone receptor interactor 11 (CEV14) gene fusion was confirmed via reverse transcription-polymerase chain reaction (RT-PCR), which additionally revealed the chromosome rearrangement t(5;14)(q33;q32). Due to the correlation between PDGFRß-CEV14 expression and effectiveness of treatment with tyrosine kinase inhibitors, this fusion gene is considered to be an oncogene. In the present study, an elderly patient was diagnosed with a myeloid tumor associated with the fusion gene PDGFRß-CEV14, using the methods of FISH and RT-PCR. These methods were confirmed to be of significant value in improving diagnosis, guiding treatment and increasing the cure rate of patients, due to their ability to detect multiple rearrangement genes associated with PDGFRß in myelodysplastic and myeloproliferative neoplasms.
RESUMEN
OBJECTIVE: To assess the diagnostic value of narrow-band imaging with magnifying endoscopy (NBI-ME) for early gastric cancer (EGC). METHODS: We searched PubMed, Embase, Web of Science and the Cochrane Library for literature of NBI-ME in diagnosis of EGC, and then performed meta-analysis. RESULTS: A total of 12 articles involving 2 278 samples from 2 048 patients were included. The overall sensitivity of NBI-ME for diagnosis of EGC was 0.84 [95% CI: 0.80~0.87], specificity was 0.96 (95% CI: 0.95~0.97),and area under the symmetric receiver operator characteristic curve (AUC) was 0.9592. The AUC value of the NBI-ME plus conventional white light endoscopy (C-WLE) subgroup (0.9706) was higher than that of NBI-ME alone (0.8162). The incremental yield of NBI-ME plus C-WLE over C-WLE was significant (IY = 9.4%, P = 0.011), while NBI-ME alone over C-WLE was not significant (IY = 0.8%, P = 0.498). CONCLUSIONS: The results show that NBI-ME plus C-WLE is an effective and preferable method for diagnosis of EGC; however, NBI-ME alone is not superior to C-WLE.
Asunto(s)
Detección Precoz del Cáncer , Gastroscopía/métodos , Imagen de Banda Estrecha , Neoplasias Gástricas/diagnóstico , Humanos , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: To investigate the relationship between surface expression of CD66c and the breakpoint cluster region-Abelson (BCR-ABL1) fusion gene in B-acute lymphoblastic leukemia (B-ALL) at primary diagnosis, and their concordance during minimal residual disease (MRD) monitoring. METHODS: Bone marrow biopsies were collected from newly diagnosed B-ALL patients (n = 43) between September 2011 and September 2014. Karyotyping was used to detect Philadelphia chromosome (Ph), and fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect BCR-ABL1 fusion gene. Immunophenotyping was performed by flow cytometry for leukemia. Patients with both CD66c expression and BCR-ABL1 were further assessed for MRD during treatment. RESULTS: Overall, 26/43 (60.5%) B-ALL patients were positive for BCR-ABL1 fusion gene expression, and all Ph positive cases (17/43; 39.5%) expressed BCR-ABL1 and CD66c. CD66c was expressed at significantly higher levels in BCR-ABL1 positive than negative patients (24/26, 92.3% vs. 11/17, 64.7%; P = 0.042), and furthermore, in all Ph positive cases (17/17, 100% vs. 18/26, 69.2%; P = 0.014). When BCR-ABL1 was set as the gold standard for the presence or absence of MRD after treatment, both CD66c alone and the MRD panel including CD66c demonstrated high diagnostic performance for the detection of MRD, with values of area under the receptor operation curve (ROC) of 0.881 vs. 0.891 respectively. CONCLUSIONS: The stable expression pattern of CD66c has noteworthy clinical value in B-ALL not only in the recognition of abnormal leukemia cells at primary diagnosis but also in monitoring of MRD during the treatment, especially in patients without definitely cytogenetic or molecular abnormal, and thus, warrants further investigation as a routine clinical marker for MRD detection by flow cytometry.
RESUMEN
In diabetic patients, left ventricular (LV) remodeling is highly prevalent; however, little is known about the impact of diabetes on right ventricular (RV) structure and function. We recently found that overexpression of angiotensin (ANG)-converting enzyme 2 (ACE2), which metabolizes ANG-II to ANG-(1-7) and ANG-I to ANG-(1-9), may improve LV remodeling in diabetic cardiomyopathy (DCM). Here, we aimed to assess whether LV remodeling and dysfunction are paralleled by RV alterations and the effects of ANG-(1-7) on RV remodeling in DCM. After 12 wk of diabetes induced by a single intraperitoneal injection of streptozotocin, rats were treated with saline, ANG-(1-7), perindopril, ANG-(1-7) plus perindopril, ANG-(1-7) plus Mas receptor antagonist A779, or ANG-(1-7) plus ANG-II type 2 receptor antagonist PD123319 for 4 wk. RV remodeling in diabetic rats was indicated by fibrosis of the RV free wall in the absence of hypertrophy and apoptosis. Treatment with ANG-(1-7) prevented diabetes-induced RV fibrosis and dysfunction. ANG-(1-7) (800 ng·kg(-1)·min(-1)) was superior to perindopril in improving RV fibrosis. The major mechanisms involved a complex interaction of ANG-II type 2 and Mas receptors for subsequent downregulation of ACE expression and activity and ANG-II type 1 receptor expression, as well as upregulation of ACE2 expression and activity and the expression of ANG-II type 2 receptor and sarco(endo)plasmic reticulum Ca(2+)-ATPase. Thus RV fibrosis and dysfunction plays a central role in DCM, and ANG-(1-7) mitigates diabetes-induced RV alterations.
Asunto(s)
Angiotensina I/farmacología , Cardiomiopatías Diabéticas/tratamiento farmacológico , Ventrículos Cardíacos/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Disfunción Ventricular Derecha/prevención & control , Función Ventricular Derecha/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Animales , Glucemia/metabolismo , Células Cultivadas , Técnicas de Cocultivo , Colágeno/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 1/complicaciones , Cardiomiopatías Diabéticas/sangre , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/patología , Cardiomiopatías Diabéticas/fisiopatología , Fibrosis , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Lípidos/sangre , Masculino , Estrés Oxidativo/efectos de los fármacos , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/efectos de los fármacos , Proteínas Proto-Oncogénicas/metabolismo , Ratas Wistar , Receptor de Angiotensina Tipo 2/efectos de los fármacos , Receptor de Angiotensina Tipo 2/metabolismo , Receptores Acoplados a Proteínas G/efectos de los fármacos , Receptores Acoplados a Proteínas G/metabolismo , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Factor de Crecimiento Transformador beta1/metabolismo , Disfunción Ventricular Derecha/sangre , Disfunción Ventricular Derecha/etiología , Disfunción Ventricular Derecha/patología , Disfunción Ventricular Derecha/fisiopatologíaRESUMEN
We retrospectively analyzed 449 patients with AML under the WHO classification of AML 2008 and probed implications of this classification in diagnosis and treatment of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) among them. The clinical presentations, biological features, treatments, and prognosis of patients diagnosed with AML-MRC were analyzed and compared with those of AML not otherwise specified (AML-NOS). In all patients, 115 (25.6%) were diagnosed as AML-MRC including 64 males and 51 females with median onset age of 48 years (range from 17 to 78). Their complete remission (CR) rate was 60.9% and relapse rate was 57.1%. The observed median overall survival (OS) and disease-free survival (DFS) were 10 and 5 months, respectively, which was significantly shorter than those of AML-NOS patients (P < 0.05). The prognosis of AML-MRC patients with myelodysplastic syndrome (MDS)-related cytogenetics sole was similar to those with history of MDS or myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Patients with MDS-related cytogenetic abnormalities and/or history of MDS or MDS/MPN predisposed significantly shortened CR, OS, and DFS than AML-MRC patients with only multilineage dysplasia (MLD) and AML-NOS patients (P < 0.05). Multivariate analysis showed that age, cytogenetics, and history of MDS or MDS/MPN were independent prognostic factors. Patient diagnosed as AML-MRC presented distinctive clinical and biological features. Presence of MLD does not change the prognosis.