RESUMO
Sézary syndrome (SS) is an incurable leukemic variant of cutaneous T-cell lymphoma and its pathogenesis is still unknown. Diagnosis/prognosis may strongly ameliorate the management of SS individuals. Here, we profiled the expression of 470 microRNAs (miRNAs) in a cohort of 22 SS patients, and we identified 45 miRNAs differentially expressed between SS and controls. Using predictive analysis, a list of 19 miRNAs, including miR-21, miR-214, miR-486, miR-18a, miR-342, miR-31 and let-7 members were also found. Moreover, we defined a signature of 14 miRNAs including again miR-21, potentially able to discriminate patients with unfavorable and favorable outcome. We validated our data for miR-21, miR-214 and miR-486 by qRT-PCR, including an additional set of array-independent SS cases. In addition, we also provide an in vitro evidence for a contribution of miR-214, miR-486 and miR-21 to apoptotic resistance of CTCL cell line.
Assuntos
Biomarcadores Tumorais/genética , Sobrevivência Celular/genética , Perfilação da Expressão Gênica , MicroRNAs/genética , Síndrome de Sézary/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Nucleossomos/metabolismo , Síndrome de Sézary/metabolismo , Síndrome de Sézary/mortalidade , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/mortalidade , Linfócitos T/metabolismo , Regulação para CimaRESUMO
Overexpression of the TCL1 gene family plays a role in the onset of T-cell leukemias in mice and in humans. The Tcl1 gene is tightly regulated during early embryogenesis in which it participates in embryonic stem (ES)-cells proliferation and during lymphoid differentiation. Here, we provide evidences that Tcl1 is also important in mouse hair follicle (HF) and skin homeostasis. We found that Tcl1(-/-) adult mice exhibit hair loss, leading to alopecia with extensive skin lesions. By analysing Tcl1 expression in the wild-type (wt) skin through different stages of hair differentiation, we observe high levels in the secondary hair germ (HG) cells and hair bulges, during early anagen and catagen-telogen transition phases. The loss of Tcl1 does not result in apparent skin morphological defects during embryonic development and at birth, but its absence causes a reduction of proliferation in anagen HFs. Importantly, we show the that absence of Tcl1 induces a significant loss of the stem-cell marker CD34 (but not alpha6-integrin) expression in the bulge cells, which is necessary to maintain stem-cell characteristics. Therefore, our findings indicate that Tcl1 gene(s) might have important roles in hair formation, by its involvement in cycling and self-renewal of transient amplifying (TA) and stem-cell (SC) populations.
