Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
1.
Blood ; 140(13): 1522-1532, 2022 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-35687761

RESUMEN

Adult T-cell leukemia (ATL) is a lymphoid neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1), which encodes the transcriptional activator Tax, which participates in the immortalization of infected T cells. ATL is classified into 4 subtypes: smoldering, chronic, acute, and lymphoma. We determined whether natural killer receptors (NKRs) were expressed in ATL. NKR expression (KIR2DL1/2DS1, KIR2DL2/2DL3/2DS2, KIR3DL2, NKG2A, NKG2C, and NKp46) was assessed in a discovery cohort of 21 ATL, and KIR3DL2 was then assessed in 71 patients with ATL. KIR3DL2 was the only NKR among those studied frequently expressed by acute-type vs lymphoma- and chronic/smoldering-type ATL (36 of 40, 4 of 16, and 1 of 15, respectively; P = .001), although acute- and lymphoma-type ATL had similar mutation profiles by targeted exome sequencing. The correlation of KIR3DL2 expression with promoter demethylation was determined by microarray-based DNA methylation profiling. To explore the role of HTLV-1, KIR3DL2 and TAX messenger RNA (mRNA) expression levels were assessed by PrimeFlow RNA in primary ATL and in CD4+ T cells infected with HTLV-1 in vitro. TAX mRNA and KIR3DL2 protein expressions were correlated on ATL cells. HTLV-1 infection triggered KIR3DL2 by CD4+ cells but Tax alone did not induce KIR3DL2 expression. Ex vivo, autologous, antibody-dependent cell cytotoxicity using lacutamab, a first-in-class anti-KIR3DL2 humanized antibody, selectively killed KIR3DL2+ primary ATL cells ex vivo. To conclude, KIR3DL2 expression is associated with acute-type ATL. Transcription of KIR3DL2 may be triggered by HTLV-1 infection and correlates with hypomethylation of the promoter. The benefit of targeting KIR3DL2 with lacutamab is being further explored in a randomized phase 2 study in peripheral T-cell lymphoma, including ATL (registered on https://clinicaltrials.gov as #NCT04984837).


Asunto(s)
Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Adulto , Productos del Gen tax/genética , Productos del Gen tax/metabolismo , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/genética , Virus Linfotrópico T Tipo 1 Humano/genética , Virus Linfotrópico T Tipo 1 Humano/metabolismo , Humanos , Leucemia-Linfoma de Células T del Adulto/patología , ARN , ARN Mensajero , Receptores KIR3DL2/genética
2.
Anticancer Drugs ; 32(10): 1118-1122, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34145177

RESUMEN

Myeloid sarcomas represent a heterogeneous group of diseases with a tumoral presentation of acute myeloid leukemia. The clinical presentation of these hematologic cancers is typically aggressive and thus rapidly fatal in the absence of treatment, which relies on intensive chemotherapy that is sometimes followed by allogeneic hematopoietic stem-cell transplant (AHSCT). However, the global treatment strategy for these lesions is currently not well established. We report the case of a patient presenting with a highly refractory mediastinal myeloid sarcoma with uncommon morphologic and phenotypic characteristics and a clonal TCR rearrangement. The patient's disease was progressive despite multiple courses of intensive chemotherapy and a combination of nelarabine and venetoclax finally led to a complete metabolic response consolidated by an AHSCT. This treatment regimen, which has never been reported before, was very well tolerated especially on the neurologic and hematologic levels. This case underlines the clinical, histologic and molecular heterogeneity of what is called myeloid sarcoma and the importance of next-generation sequencing analysis of the tumor mass with both myeloid and lymphoid panels to better classify this rare entity and identify therapeutic targets.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Mediastino/tratamiento farmacológico , Neoplasias del Mediastino/patología , Sarcoma Mieloide/tratamiento farmacológico , Sarcoma Mieloide/patología , Antineoplásicos/uso terapéutico , Arabinonucleósidos/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Persona de Mediana Edad , Sulfonamidas/uso terapéutico
3.
J Cell Physiol ; 233(2): 958-967, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28387421

RESUMEN

Psoriasis vulgaris is a common skin inflammatory disease characterized by recurrent flare episodes associated with scaly well-demarcated skin plaques. Skin biopsies from psoriatic patients with high PASI score (22.67 ± 8.67) and from HD were used to study APN/CD13. APN/CD13 is over-expressed in LP and nLP compare to HD skins and fibroblasts. This over-expression is positively correlated with specific enzymatic activity enhancement. However, discrepancies between APN/CD13 expression in LP and nLP prompt us to focus our study on APN/CD13 modulation. Calcitonin Gene Related Peptide (CGRP), a neuropeptide, positively modulated expression and activity of APN/CD13. CGRP consistently induced IL4 secretion, which is also involved in the increase of APN/CD13 expression and activity, which is significantly reversed using IL-4 blocking antibody. Surprisingly, retinoic acid altered the APN/CD13 enzymatic activity only in nLP fibroblasts without modification of APN/CD13 expression. APN/CD13 is over-expressed on psoriatic fibroblasts and exerted high level of activity compare to HD fibroblasts. Taken together, several factors such as CGRP and IL-4 acted on positive regulation of APN/CD13 expression and activity. This study highlighted the interest of APN/CD13 as a new potential target, which should be investigated in psoriasis.


Asunto(s)
Antígenos CD13/metabolismo , Péptido Relacionado con Gen de Calcitonina/farmacología , Fibroblastos/efectos de los fármacos , Interleucina-4/farmacología , Psoriasis/enzimología , Piel/efectos de los fármacos , Tretinoina/farmacología , Adulto , Anciano , Antígenos CD13/genética , Estudios de Casos y Controles , Células Cultivadas , Femenino , Fibroblastos/enzimología , Fibroblastos/patología , Humanos , Masculino , Persona de Mediana Edad , Psoriasis/genética , Psoriasis/patología , Piel/enzimología , Piel/patología , Factores de Tiempo , Regulación hacia Arriba
4.
Int J Surg Pathol ; 32(1): 150-154, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37157817

RESUMEN

EBV-positive inflammatory follicular dendritic cell sarcoma (EBV+ inflammatory FDCS) is a rare neoplasm almost exclusively located in the spleen or liver. It is characterized by a proliferation of EBV-positive spindle-shaped cells bearing follicular dendritic cell markers, associated with an abundant lymphoplasmacytic infiltrate. EBV+ inflammatory FDCS is often asymptomatic or responsible for mild symptoms. It usually displays an indolent course and its prognosis is excellent after tumor removal, although relapsing and metastatic forms exist. Herein, we describe an aggressive form of splenic EBV+ inflammatory FDCS in a 79-year-old woman presenting with abdominal pain, deterioration of general health status, major inflammatory syndrome, and symptomatic hypercalcemia. A splenectomy was performed leading to a rapid improvement in her clinical condition and normalization of laboratory abnormalities. Unfortunately, her symptoms and laboratory abnormalities reappeared 4 months later. Computed tomography showed a mass in the splenectomy site and multiple liver and peritoneal nodules. Further analyses were performed on tumor tissue and showed positive phospho-ERK staining of tumoral cells indicating activation of MAPK pathway. Inactivating mutations were found on CDKN2A and NF1 genes. Subsequently, the patient's condition deteriorated rapidly. Since interleukin-6 levels were dramatically increased, tocilizumab was used but only had a transient effect on the patient's symptoms and inflammatory syndrome. Antitumor agent gemcitabine was initiated but her clinical condition continued to deteriorate and the patient died 2 weeks later. The management of aggressive forms of EBV+ inflammatory FDCS remains challenging. However, since these tumors seem to display genetic alterations, better characterization could lead to molecular targeted therapies.


Asunto(s)
Sarcoma de Células Dendríticas Foliculares , Neoplasias de los Tejidos Blandos , Femenino , Humanos , Anciano , Sarcoma de Células Dendríticas Foliculares/diagnóstico , Sarcoma de Células Dendríticas Foliculares/genética , Sarcoma de Células Dendríticas Foliculares/metabolismo , Bazo/patología , Herpesvirus Humano 4/genética , Recurrencia Local de Neoplasia/patología , Células Dendríticas Foliculares/metabolismo , Células Dendríticas Foliculares/patología , Neoplasias de los Tejidos Blandos/patología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA