RESUMO
Oral verrucous hyperplasia (OVH) refers to a whitish or pink elevated plaque or mass on the oral mucosa with either verrucous or papillary surface. Given its potential of malignant transformation, it is crucial to pursue aggressive treatment and close surveillance to the lesion. Herein, we present a case of a 43-year-old male patient with large area OVH on the left buccal mucosa who was successfully treated using diode laser ablation combined with 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT). After two sessions of treatment, the lesions regressed completely, and no recurrence was observed at the 18-month follow-up. Therefore, diode laser ablation combined with ALA-PDT may be an efficient and safe treatment modality for large area OVH.
Assuntos
Terapia a Laser , Neoplasias Bucais , Fotoquimioterapia , Masculino , Humanos , Adulto , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias Bucais/tratamento farmacológico , Hiperplasia/complicações , Hiperplasia/tratamento farmacológico , Fotoquimioterapia/métodos , Resultado do Tratamento , Ácido Aminolevulínico/uso terapêutico , Terapia a Laser/efeitos adversosRESUMO
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy often associated with poor outcomes. To identify high-risk factors and potential actionable targets for T-ALL, we perform integrated genomic and transcriptomic analyses on samples from 165 Chinese pediatric and adult T-ALL patients, of whom 85% have outcome information. The genomic mutation landscape of this Chinese cohort is very similar to the Western cohort published previously, except that the rate of NOTCH1 mutations is significant lower in the Chinese T-ALL patients. Among 47 recurrently mutated genes in 7 functional categories, we identify RAS pathway and PTEN mutations as poor survival factors for non-TAL and TAL subtypes, respectively. Mutations in the PI3K pathway are mutually exclusive with mutations in the RAS and NOTCH1 pathways as well as transcription factors. Further analysis demonstrates that approximately 43% of the high-risk patients harbor at least one potential actionable alteration identified in this study, and T-ALLs with RAS pathway mutations are hypersensitive to MEKi in vitro and in vivo. Thus, our integrated genomic analyses not only systematically identify high-risk factors but suggest that these high-risk factors are promising targets for T-ALL therapies.
RESUMO
3D genome alternations can dysregulate gene expression by rewiring enhancer-promoter interactions and lead to diseases. We report integrated analyses of 3D genome alterations and differential gene expressions in 18 newly diagnosed T-lineage acute lymphoblastic leukemia (T-ALL) patients and 4 healthy controls. 3D genome organizations at the levels of compartment, topologically associated domains and loop could hierarchically classify different subtypes of T-ALL according to T cell differentiation trajectory, similar to gene expressions-based classification. Thirty-four previously unrecognized translocations and 44 translocation-mediated neo-loops are mapped by Hi-C analysis. We find that neo-loops formed in the non-coding region of the genome could potentially regulate ectopic expressions of TLX3, TAL2 and HOXA transcription factors via enhancer hijacking. Importantly, both translocation-mediated neo-loops and NUP98-related fusions are associated with HOXA13 ectopic expressions. Patients with HOXA11-A13 expressions, but not other genes in the HOXA cluster, have immature immunophenotype and poor outcomes. Here, we highlight the potentially important roles of 3D genome alterations in the etiology and prognosis of T-ALL.
Assuntos
Cromossomos/metabolismo , Proteínas de Homeodomínio/genética , Leucemia-Linfoma de Células T do Adulto/genética , Conformação Molecular , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Linfócitos T/metabolismo , Translocação Genética , Acetilação , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem Celular Tumoral , Linhagem da Célula , Criança , Sequenciamento de Cromatina por Imunoprecipitação , Cromossomos/genética , Progressão da Doença , Elementos Facilitadores Genéticos , Perfilação da Expressão Gênica , Regulação Leucêmica da Expressão Gênica/genética , Regulação Leucêmica da Expressão Gênica/imunologia , Ontologia Genética , Hematopoese/genética , Histonas/metabolismo , Proteínas de Homeodomínio/metabolismo , Humanos , Imunofenotipagem , Leucemia-Linfoma de Células T do Adulto/metabolismo , Leucemia-Linfoma de Células T do Adulto/mortalidade , Leucemia-Linfoma de Células T do Adulto/patologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Prognóstico , Linfócitos T/patologia , Adulto JovemRESUMO
Leukemia stem cells (LSCs) are regarded as the origins and key therapeutic targets of leukemia, but limited knowledge is available on the key determinants of LSC 'stemness'. Using single-cell RNA-seq analysis, we identify a master regulator, SPI1, the LSC-specific expression of which determines the molecular signature and activity of LSCs in the murine Pten-null T-ALL model. Although initiated by PTEN-controlled ß-catenin activation, Spi1 expression and LSC 'stemness' are maintained by a ß-catenin-SPI1-HAVCR2 regulatory circuit independent of the leukemogenic driver mutation. Perturbing any component of this circuit either genetically or pharmacologically can prevent LSC formation or eliminate existing LSCs. LSCs lose their 'stemness' when Spi1 expression is silenced by DNA methylation, but Spi1 expression can be reactivated by 5-AZ treatment. Importantly, similar regulatory mechanisms may be also present in human T-ALL.