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1.
Br J Haematol ; 205(1): 256-267, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38811025

RESUMEN

European LeukemiaNet refined their risk classification of acute myeloid leukaemia (AML) in 2022 (ELN 2022) according to the two new myeloid classifications published the same year. We have retrospectively assessed the prognostic value of the ELN 2022 in 120 AML patients undergoing allogeneic haematopoietic cell transplantation (allo-HCT), including 99 in first complete response (CR1) from 2011 to 2021 in our centre. Adverse risk patients (Adv) presented inferior outcome in terms of overall survival (OS) and leukaemia-free survival (LFS) (OS [p = 0.003], LFS [p = 0.02]), confirmed in multivariate analysis (hazard ratio [HR] for OS = 2.00, p = 0.037). These results were also seen in patients allografted in CR1. Further analysis identified a subgroup named adverse-plus (AdvP), including complex karyotype, MECOM(EVI1) rearrangements and TP53 mutations, with worse outcomes than the rest of groups of patients, including the Adv (HR for OS: 3.14, p < 0.001, HR for LFS: 3.36, p < 0.001), with higher 2-year cumulative incidence of relapse (p < 0.001). Notably, within this analysis, the outcome of Adv and intermediate patients were similar. These findings highlight the prognostic value of ELN 2022 in patients undergoing allo-HCT, which can be improved by the recognition of a poor genetic subset (AdvP) within the Adv risk group.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Adulto , Pronóstico , Anciano , Estudios Retrospectivos , Trasplante Homólogo , Adolescente , Adulto Joven , Mutación , Medición de Riesgo/métodos , Supervivencia sin Enfermedad , Proteína del Locus del Complejo MDS1 y EV11/genética
2.
Mult Scler Relat Disord ; 84: 105501, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38401203

RESUMEN

BACKGROUND: Standardizing health outcomes is challenging in clinical management, but it also holds the potential for creating a healthcare system that is both more effective and efficient. The aim of the present study is to define a standardized set of health outcomes for managing Relapsing-Remitting Multiple Sclerosis (RRMS). METHODS: The project was led and coordinated by a multidisciplinary scientific committee (SC), which included a literature review, a patient-focused group, three nominal group meetings, and two SC meetings. RESULTS: 36 outcome variables were included in the standard set: 24 clinical (including weight, smoking habit, comorbidities, disability, mobility, diagnosis of secondary progressive multiple sclerosis, relapsed-related variables, radiological variables, cognitive status and disease-related symptoms), nine treatment-related (pharmacological and non-pharmacological information), and 3 related to the impact of RRMS on the patient's life (quality of life, pregnancy desire, work-related difficulties). In addition, experts also agreed to collect 10 case-mix variables that may affect but cannot be controlled as part of the management of the condition: 4 sociodemographic (age, sex, race, and employment status) and 6 clinical (height, date of diagnosis and first episode, serological status, early symptoms, and number of relapses pre-diagnosis). CONCLUSION: The information provided through the present standard set of outcome variables can improve the management of RRMS and promote patient-centred quality care.


Asunto(s)
Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/terapia , Calidad de Vida , Evaluación de Resultado en la Atención de Salud
3.
Cancers (Basel) ; 16(4)2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38398096

RESUMEN

Non-acute myeloid neoplasms (MNs) with NPM1 mutations (NPM1mut-MNs) pose a diagnostic and therapeutic dilemma, primarily manifesting as chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS). The classification and treatment approach for these conditions as acute myeloid leukemia (AML) are debated. We describe eight cases of atypical NPM1mut-MNs from our institution and review the literature. We include a rare case of concurrent prostate carcinoma and MN consistent with chronic eosinophilic leukemia, progressing to myeloid sarcoma of the skin. Of the remaining seven cases, five were CMML and two were MDS. NPM1 mutations occur in 3-5% of CMML and 1-6% of MDS, with an increased likelihood of rapid evolution to AML. Their influence on disease progression varies, and their prognostic significance in non-acute MNs is less established than in AML. Non-acute MNs with NPM1 mutations may display an aggressive clinical course, emphasizing the need for a comprehensive diagnosis integrating clinical and biological data. Tailoring patient management on an individualized basis, favoring intensive treatment aligned with AML protocols, is crucial, regardless of blast percentage. Research on the impact of NPM1 mutations in non-acute myeloid neoplasms is ongoing, requiring challenging prospective studies with substantial patient cohorts and extended follow-up periods for validation.

4.
Ann Hematol ; 103(3): 737-747, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38263537

RESUMEN

To elucidate the role of splanchnic vein thrombosis (SVT) and genomic characteristics in prognosis and survival, we compared patients with polycythemia vera (PV) or essential thrombocythemia (ET) presenting SVT at diagnosis (n = 69, median age 43 years) or during follow-up (n = 21, median age 46 years) to a sex- and age-matched control group of PV/ET without SVT (n = 165, median age 48 years). The majority of patients presenting with SVT at diagnosis were classified as myeloproliferative neoplasm with heterozygous JAK2 mutation (87% of cases vs. 69% in PV/ET control group, p < 0.05), characterized by low JAK2 allele burden and no high-risk mutations. Despite this lower molecular complexity, patients presenting with SVT showed a higher risk of death (HR 3.0, 95% CI 1.5-6.0, p = 0.003) and lower event-free survival (HR 3.0, 95% CI 1.9-4.8, p < 0.001) than age- and sex-matched PV/ET controls. In patients presenting with SVT, molecular high-risk was associated with increased risk of venous re-thrombosis (HR 5.8, 95% CI 1.4-24.0, p = 0.01). Patients developing SVT during follow-up were more frequently allocated in molecular high-risk than those with SVT at diagnosis (52% versus 13%, p < 0.05). In the whole cohort of patients, molecular classification identified PV/ET patients at higher risk of disease progression whereas DNMT3A/TET2/ASXL1 mutations were associated with higher risk of arterial thrombosis. In conclusion, clinical and molecular characteristics are different in PV/ET patients with SVT, depending on whether it occurs at diagnosis or at follow-up. Molecular characterization by NGS is useful for assessing the risk of thrombosis and disease progression in young patients with PV/ET.


Asunto(s)
Policitemia Vera , Trombocitemia Esencial , Trombosis , Trombosis de la Vena , Humanos , Adulto , Persona de Mediana Edad , Policitemia Vera/complicaciones , Policitemia Vera/genética , Policitemia Vera/diagnóstico , Trombocitemia Esencial/complicaciones , Trombocitemia Esencial/genética , Trombocitemia Esencial/diagnóstico , Trombosis de la Vena/genética , Trombosis/etiología , Trombosis/genética , Genómica , Progresión de la Enfermedad , Janus Quinasa 2/genética
5.
Br J Haematol ; 204(3): 892-897, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38013238

RESUMEN

Recently modified diagnostic criteria for chronic myelomonocytic leukaemia (CMML) have lowered the cut-off for absolute monocytosis. In the largest series to date, we have analysed 313 CMML patients, including 104 with oligomonocytic (OM)-CMML. Five-year survival was longer for OM-CMML than for other patients (p < 0.001). Multivariate analysis identified OM-CMML as a favourable prognostic factor (HR 0.58; p = 0.002). The 5-year cumulative incidence of progression to classical CMML was 47%. Older age and transfusion dependence were adverse prognostic factors for OM-CMML. Our results support the inclusion of OM-CMML in the CMML category as a subtype with superior outcomes.


Asunto(s)
Leucemia Mielomonocítica Crónica , Humanos , Leucemia Mielomonocítica Crónica/diagnóstico , Leucocitosis , Pronóstico
6.
Leukemia ; 38(3): 557-569, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38017105

RESUMEN

Chronic lymphocytic leukemia (CLL) is a B-cell neoplasm with a heterogeneous clinical behavior. In 5-10% of patients the disease transforms into a diffuse large-B cell lymphoma known as Richter transformation (RT), which is associated with dismal prognosis. Here, we aimed to establish patient-derived xenograft (PDX) models to study the molecular features and evolution of CLL and RT. We generated two PDXs by injecting CLL (PDX12) and RT (PDX19) cells into immunocompromised NSG mice. Both PDXs were morphologically and phenotypically similar to RT. Whole-genome sequencing analysis at different time points of the PDX evolution revealed a genomic landscape similar to RT tumors from both patients and uncovered an unprecedented RT subclonal heterogeneity and clonal evolution during PDX generation. In PDX12, the transformed cells expanded from a very small subclone already present at the CLL stage. Transcriptomic analysis of PDXs showed a high oxidative phosphorylation (OXPHOS) and low B-cell receptor (BCR) signaling similar to the RT in the patients. IACS-010759, an OXPHOS inhibitor, reduced proliferation, and circumvented resistance to venetoclax. In summary, we have generated new RT-PDX models, one of them from CLL cells that mimicked the evolution of CLL to RT uncovering intrinsic features of RT cells of therapeutical value.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Linfoma de Células B Grandes Difuso , Humanos , Animales , Ratones , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/patología , Xenoinjertos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Evolución Clonal/genética , Pronóstico , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología
8.
Gels ; 9(12)2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38131954

RESUMEN

Nanofibrous materials present interesting characteristics, such as higher area/mass ratio and reactivity. These properties have been exploited in different applications, such as drug-controlled release and site-specific targeting of biomolecules for several disease treatments, including cancer. The main goal of this study was to develop magnetized nanofiber systems of lysozyme (Lys) for biological applications. The system envisaged electrospun polyvinyl alcohol (PVA) and PVA/chitosan (CS) nanofibers, loaded with Lys, crosslinked with boronic acids [phenylboronic acid (PBA), including 2-acetylphenylboronic acid (aPBA), 2-formylphenylboronic (fPBA), or bortezomib (BTZ)] and functionalized with magnetic nanobeads (IONPs), which was successfully built and tested using a microscale approach. Evaluation of the morphology of nanofibers, obtained by electrospinning, was carried out using SEM. The biological activities of the Lys-loaded PVA/CS (90:10 and 70:30) nanofibers were evaluated using the Micrococcus lysodeikticus method. To evaluate the success of the encapsulation process, the ratio of adsorbed Lys on the nanofibers, Lys activity, and in vitro Lys release were determined in buffer solution at pH values mimicking the environment of cancer cells. The viability of Caco-2 cancer cells was evaluated after being in contact with electrospun PVA + Lys and PVA/CS + Lys nanofibers, with or without boronic acid functionalation, and all were magnetized with IONPs.

10.
Ann Rheum Dis ; 82(12): 1594-1605, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37666646

RESUMEN

BACKGROUND: The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. OBJECTIVES: To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. METHODS: Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. RESULTS: Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. CONCLUSION: Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms.


Asunto(s)
Artritis , Mosaicismo , Adulto , Humanos , Masculino , Femenino , Citocinas/genética , Ferritinas , Glucocorticoides , Mutación
11.
Biodivers Data J ; 11: e108596, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37680444

RESUMEN

Background: The Herpetology Collection of the Natural History Museum Gustavo Orcés V. at Escuela Politécnica Nacional (MEPN-H) in Quito maintains more than sixteen thousand curated specimens and it comprises Ecuador ´s second largest collection of herps. New information: The Collection contains 193 type specimens: 14 holotypes, 34 paratopotypes and 145 paratypes, which correspond to 10 families, 17 genera and 32 species. The collection of type specimens is particularly important in the genera Atelopus and Pristimantis in amphibians and the genera Atractus and Enyaloides in reptiles. An assessment of the geographic distribution showed that collection sites of type specimens are clustered towards the south of Ecuador in the provinces of Zamora Chinchipe, Morona Santiago and Pastaza in the Amazon Region; and in the provinces of Carchi and Azuay in the Andes. The collection of type specimens dates from 1955 to 2013, comprising an invaluable source of historical biodiversity data.

13.
Cancers (Basel) ; 15(15)2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37568719

RESUMEN

Myelofibrosis (MF) is a heterogeneous disease regarding its mutational landscape, clinical presentation, and outcomes. The aim of our work is to evaluate the genomic classification of MF considering whether it is primary or secondary. One-hundred seventy-five patients, 81 with primary MF (PMF) and 94 with secondary MF (SMF) were hierarchically allocated into eight molecular groups. We found that TP53 disruption/aneuploidy (n = 16, 9%) was more frequent (12% versus 6%) and showed higher allele burden (57% versus 15%, p = 0.01) in SMF than in PMF, and was associated with shorter survival (median 3.5 years). Mutations in chromatin/spliceosome genes (n = 72, 41%) represented the most frequent genomic group in PMF. Homozygous JAK2 mutation (n = 40, 23%) was enriched with old patients with SMF after long-standing polycythemia vera, whereas MF with heterozygous JAK2 mutation (n = 22, 13%) was similarly distributed among PMF and SMF. MF with CALR mutation (n = 19, 11%) predominated in post-essential thrombocythemia MF. The remaining genomic groups were infrequent. TP53 disruption, chromatin/spliceosome mutation, and homozygous JAK2 mutation were associated with significantly shorter survival and higher risk of progression. In conclusion, genomic classification reveals different pathogenic pathways between PMF and SMF and provides relevant information regarding disease phenotype and outcomes.

14.
Life Sci Alliance ; 6(11)2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37562845

RESUMEN

Splicing factor 3B subunit 1 (SF3B1) is involved in pre-mRNA branch site recognition and is the target of antitumor-splicing inhibitors. Mutations in SF3B1 are observed in 15% of patients with chronic lymphocytic leukemia (CLL) and are associated with poor prognosis, but their pathogenic mechanisms remain poorly understood. Using deep RNA-sequencing data from 298 CLL tumor samples and isogenic SF3B1 WT and K700E-mutated CLL cell lines, we characterize targets and pre-mRNA sequence features associated with the selection of cryptic 3' splice sites upon SF3B1 mutation, including an event in the MAP3K7 gene relevant for activation of NF-κB signaling. Using the H3B-8800 splicing modulator, we show, for the first time in CLL, cytotoxic effects in vitro in primary CLL samples and in SF3B1-mutated isogenic CLL cell lines, accompanied by major splicing changes and delayed leukemic infiltration in a CLL xenotransplant mouse model. H3B-8800 displayed preferential lethality towards SF3B1-mutated cells and synergism with the BCL2 inhibitor venetoclax, supporting the potential use of SF3B1 inhibitors as a novel therapeutic strategy in CLL.


Asunto(s)
Antineoplásicos , Leucemia Linfocítica Crónica de Células B , Ratones , Animales , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/patología , Factores de Empalme de ARN/genética , Precursores del ARN , Fosfoproteínas/genética , Mutación/genética , Sitios de Empalme de ARN , Factores de Transcripción/genética
15.
Blood Adv ; 7(19): 5799-5811, 2023 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-37450374

RESUMEN

Germ line predisposition in acute myeloid leukemia (AML) has gained attention in recent years because of a nonnegligible frequency and an impact on management of patients and their relatives. Risk alleles for AML development may be present in patients without a clinical suspicion of hereditary hematologic malignancy syndrome. In this study we investigated the presence of germ line variants (GVs) in 288 genes related to cancer predisposition in 47 patients with available paired, tumor-normal material, namely bone marrow stroma cells (n = 29), postremission bone marrow (n = 17), and saliva (n = 1). These patients correspond to 2 broad AML categories with heterogeneous genetic background (AML myelodysplasia related and AML defined by differentiation) and none of them had phenotypic abnormalities, previous history of cytopenia, or strong cancer aggregation. We found 11 pathogenic or likely pathogenic variants, 6 affecting genes related to autosomal dominant cancer predisposition syndromes (ATM, DDX41, and CHEK2) and 5 related to autosomal recessive bone marrow failure syndromes (FANCA, FANCM, SBDS, DNAJC21, and CSF3R). We did not find differences in clinical characteristics nor outcome between carriers of GVs vs noncarriers. Further studies in unselected AML cohorts are needed to determine GV incidence and penetrance and, in particular, to clarify the role of ATM nonsense mutations in AML predisposition.


Asunto(s)
Neoplasias Hematológicas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/epidemiología , Síndromes Mielodisplásicos/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/epidemiología , Mutación de Línea Germinal , Genotipo , ADN Helicasas/genética
16.
Curr Oncol ; 30(6): 5201-5213, 2023 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-37366878

RESUMEN

In recent years, major advances in the understanding of acute myeloid leukemia (AML) pathogenesis, together with technological progress, have led us into a new era in the diagnosis and follow-up of patients with AML. A combination of immunophenotyping, cytogenetic and molecular studies are required for AML diagnosis, including the use of next-generation sequencing (NGS) gene panels to screen all genetic alterations with diagnostic, prognostic and/or therapeutic value. Regarding AML monitoring, multiparametric flow cytometry and quantitative PCR/RT-PCR are currently the most implemented methodologies for measurable residual disease (MRD) evaluation. Given the limitations of these techniques, there is an urgent need to incorporate new tools for MRD monitoring, such as NGS and digital PCR. This review aims to provide an overview of the different technologies used for AML diagnosis and MRD monitoring and to highlight the limitations and challenges of current versus emerging tools.


Asunto(s)
Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Neoplasia Residual/terapia , Pronóstico , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Mutación
17.
Blood ; 142(5): 434-445, 2023 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-37053555

RESUMEN

Posttransplant lymphoproliferative disorders (PTLDs) represent a broad spectrum of lymphoid proliferations, frequently associated with Epstein-Barr virus (EBV) infection. The molecular profile of pediatric monomorphic PTLDs (mPTLDs) has not been elucidated, and it is unknown whether they display similar genetic features as their counterpart in adult and immunocompetent (IMC) pediatric patients. In this study, we investigated 31 cases of pediatric mPTLD after solid organ transplantation, including 24 diffuse large B-cell lymphomas (DLBCLs), mostly classified as activated B cell, and 7 cases of Burkitt lymphoma (BL), 93% of which were EBV positive. We performed an integrated molecular approach, including fluorescence in situ hybridization, targeted gene sequencing, and copy number (CN) arrays. Overall, PTLD-BL carried mutations in MYC, ID3, DDX3X, ARID1A, or CCND3 resembling IMC-BL, higher mutational burden than PTLD-DLBCL, and lesser CN alterations than IMC-BL. PTLD-DLBCL showed a very heterogeneous genomic profile with fewer mutations and CN alterations than IMC-DLBCL. Epigenetic modifiers and genes of the Notch pathway were the most recurrently mutated in PTLD-DLBCL (both 28%). Mutations in cell cycle and Notch pathways correlated with a worse outcome. All 7 patients with PTLD-BL were alive after treatment with pediatric B-cell non-Hodgkin lymphoma protocols, whereas 54% of patients with DLBCL were cured with immunosuppression reduction, rituximab, and/or low-dose chemotherapy. These findings highlight the low complexity of pediatric PTLD-DLBCL, their good response to low-intensity treatment, and the shared pathogenesis between PTLD-BL and EBV-positive IMC-BL. We also suggest new potential parameters that could help in the diagnosis and the design of better therapeutic strategies for these patients.


Asunto(s)
Linfoma de Burkitt , Infecciones por Virus de Epstein-Barr , Linfoma de Células B Grandes Difuso , Trastornos Linfoproliferativos , Trasplante de Órganos , Niño , Humanos , Linfoma de Burkitt/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/genética , Herpesvirus Humano 4/genética , Hibridación Fluorescente in Situ , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/terapia , Trastornos Linfoproliferativos/genética , Trastornos Linfoproliferativos/patología , Trasplante de Órganos/efectos adversos
18.
Blood Adv ; 7(14): 3695-3709, 2023 07 25.
Artículo en Inglés | MEDLINE | ID: mdl-36995085

RESUMEN

The genetic mechanisms associated with splenic marginal zone lymphoma (SMZL) transformation are not well defined. We studied 41 patients with SMZL that eventually underwent large B-cell lymphoma transformation. Tumor material was obtained either only at diagnosis (9 patients), at diagnosis and transformation (18 patients), and only at transformation (14 patients). Samples were categorized in 2 groups: (1) at diagnosis (SMZL, n = 27 samples), and (2) at transformation (SMZL-T, n = 32 samples). Using copy number arrays and a next-generation sequencing custom panel, we identified that the main genomic alterations in SMZL-T involved TNFAIP3, KMT2D, TP53, ARID1A, KLF2, 1q gains, and losses of 9p21.3 (CDKN2A/B) and 7q31-q32. Compared with SMZL, SMZL-T had higher genomic complexity, and higher incidence of TNFAIP3 and TP53 alterations, 9p21.3 (CDKN2A/B) losses, and 6p gains. SMZL and SMZL-T clones arose by divergent evolution from a common altered precursor cell that acquired different genetic alterations in virtually all evaluable cases (92%, 12 of 13 cases). Using whole-genome sequencing of diagnostic and transformation samples in 1 patient, we observed that the SMZL-T sample carried more genomic aberrations than the diagnostic sample, identified a translocation t(14;19)(q32;q13) present in both samples, and detected a focal B2M deletion due to chromothripsis acquired at transformation. Survival analysis showed that KLF2 mutations, complex karyotype, and International Prognostic Index score at transformation were predictive of a shorter survival from transformation (P = .001; P = .042; and P = .007; respectively). In summary, SMZL-T are characterized by higher genomic complexity than SMZL, and characteristic genomic alterations that could represent key players in the transformation event.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Linfoma de Células B Grandes Difuso , Neoplasias del Bazo , Humanos , Neoplasias del Bazo/genética , Neoplasias del Bazo/diagnóstico , Neoplasias del Bazo/patología , Mutación , Translocación Genética , Linfoma de Células B Grandes Difuso/genética , Leucemia Linfocítica Crónica de Células B/genética
19.
Rev. medica electron ; 45(1)feb. 2023.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1442024

RESUMEN

Introducción: las interferencias oclusales no controladas precozmente pueden producir desviación de la mandíbula en sentido anteroposterior o transversal. El manejo de las mordidas cruzadas se debe iniciar en el momento del diagnóstico, preferiblemente en edades tempranas, con el fin de tratarlas en el nivel primario de prevención. Objetivo: determinar el comportamiento de la maloclusión funcional causada por interferencias oclusales en niños con dentición mixta de la Escuela Primaria Mártires del Corynthia, entre octubre de 2019 y junio de 2021. Materiales y métodos: se realizó un estudio observacional descriptivo de corte transversal en la Escuela Primaria Mártires del Corynthia, del Área de Salud José Jacinto Milanés, del municipio de Matanzas, entre octubre de 2019 y junio de 2021. El universo estuvo conformado por 66 niños. Se utilizó una planilla de recolección de datos y se solicitó el consentimiento informado a los tutores de los niños. Resultados: las edades donde los niños presentaron mayor afectación fueron de 6 a 7 años y de 8 a 9 años, ambos rangos con un 10,6 %. El 27,3 % presentó interferencias oclusales y mordida cruzada posterior unilateral. El 48,5 % fue del sexo femenino y el 30,3 % tenían edades de 6 a 7 años. El 71,2 % eran simétricos y presentaron mordida cruzada posterior unilateral. Los simétricos y con línea media coincidente representaron un 36,4 %. Conclusiones: la maloclusión funcional más frecuente en niños con dentición mixta fue la mordida cruzada posterior unilateral, que se relacionó de manera directa con las interferencias oclusales. Las asimetrías faciales y la línea media desviada estuvieron asociadas a dicha maloclusión.


Introduction: early uncontrolled occlusal interferences can produce anterior-posterior jaw deflection. Management of cross-bites should be initiated at the time of diagnosis, preferably at early ages, in order to treat them at the primary level of prevention. Objective: to determine the behavior of functional malocclusion caused by occlusal interferences in children with mixed dentition from the Martires del Corynthia primary school between October 2019 and June 2021. Materials and methods: a cross-sectional, observational, descriptive study was carried out at the Martires del Corynthia Primary School, of the Jose Jacinto Milanes Health Area, Matanzas municipality, between October 2019 and June 2021. The universe consisted of 66 children. A data collection form was used and informed consent was requested from the children's guardians. Results: the ages where the children presented more affectation were from 6 to 7 years and from 8 to 9 years, both ranges with 10.6%. 27.3% presented occlusal interferences and posterior unilateral cross-bite. 48.5% were female and 30.3% were 6 to 7 years old. 71.2% were symmetrical and presented unilateral posterior cross-bite. Symmetric patients and with a coincident midline represented 36.4%. Conclusions: the most frequent functional malocclusion in children with mixed dentition was the unilateral posterior cross-bite, which was related to occlusal interferences in a direct way. Facial asymmetries and a deviated midline were associated with the before mentioned malocclusion.

20.
Braz J Otorhinolaryngol ; 89(1): 3-13, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-34462203

RESUMEN

INTRODUCTION: Reading is a highly refined skill that encompasses two main components: decoding graphic symbols and understanding the written message. These aspects generally develop together, but reading comprehension is a much more complex process, sustained not only by the identification of written words and vocabulary but also by language systems, such as syntax and general knowledge. Although there is a well-established technique for performing the phoniatric assessment, there is no common use of tests that assess reading comprehension or the association of this information with other assessment data. OBJECTIVE: The objective of this study is, in the context of the phoniatric consultation, to evaluate the reading and retelling in children with relevant reading difficulties and to correlate the decoding and comprehension problems with the alterations observed in auditory and visual perceptual tests, pointing out the evidence that best contributed to the differential diagnosis of these subjects. METHODS: Starting from a population of 301 children enrolled in the 4th and 5th grades of elementary school, 13 children with evident reading and writing difficulties were evaluated regarding the reading and retelling tasks and separated into groups according to the problem of decoding, fluency, and comprehension. Reading performance was correlated with the performance in visual and auditory perceptual tests and based on the similarity analysis, the tests considered to be the most relevant in the diagnosis process of these children were identified. RESULT: The results suggest that the tasks: naming of figures, repetition of numbers in reverse order, figure copying, syllabic synthesis, phonemic synthesis, rhyme, and phonemic manipulation altogether contribute to diagnosis and multidisciplinary intervention aspects. CONCLUSION: Some tasks are more relevant to the diagnostic process of children with complaints of learning difficulties in reading.


Asunto(s)
Dislexia , Lectura , Niño , Humanos , Comprensión , Estudiantes , Vocabulario
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