| Texto completo | |
| Autor(es): |
Ruckert, Mariana Tannus
[1, 2]
;
Brouwers-Vos, Annet Z.
[2]
;
Nagano, Luis Fernando P.
[1]
;
Schuringa, Jan Jacob
[2]
;
Silveira, Vanessa Silva
[1]
Número total de Autores: 5
|
| Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto, SP - Brazil
[2] Univ Groningen, Univ Med Ctr Groningen, Dept Expt Hematol, Groningen - Netherlands
Número total de Afiliações: 2
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Cancer Gene Therapy; v. 27, n. 10-11 JUL 2020. |
| Citações Web of Science: | 0 |
| Resumo | |
Acute myeloid leukemia (AML) is a poor prognosis hematopoietic malignance characterized by abnormal proliferation and differentiation of hematopoietic stem cells (HSCs). Although advances in treatment have greatly improved survival rates in young patients, in the elderly population, similar to 70% of patients present poor prognosis. A pan-cancer analysis on the TCGA cohort showed that AML has the second higher HUWE1 expression in tumor samples among all cancer types. In addition, pathway enrichment analysis pointed to RAS signaling cascade as one of the most important pathways associated to HUWE1 expression in this particular AML cohort. In silico analysis for biological processes enrichment also revealed that HUWE1 expression is correlated with 13 genes involved in myeloid differentiation. Therefore, to understand the role of HUWEl in human hematopoietic stem and progenitor cells (HSPC) we constitutively expressed KRAS(G12v) oncogene concomitantly to HUWE1 knockdown in stromal co-cultures. The results showed that, in the context of KRAS(G12v), HUWE1 significantly reduces cell cumulative growth and changes myeloid differentiation profile of HSPCs. Overall, these observations suggest that HUWE1 might contribute to leukemic cell proliferation and impact myeloid differentiation of human HSCs, thus providing new venues for RAS-driven leukemia targeted therapy approach. (AU) | |
| Processo FAPESP: | 15/10694-5 - Atividade de proteínas fosfatases de dupla especificidade (DUSPs) no controle da ativação de MAP quinases: impacto na reprogramação metabólica do adenocarcinoma ductal pancreático |
| Beneficiário: | Vanessa da Silva Silveira |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |
| Processo FAPESP: | 15/12146-5 - Investigação do papel da ubiquitina-ligase HUWE1 na modulação da via de sinalização RAS em modelos leucêmicos |
| Beneficiário: | Mariana Tannús Ruckert |
| Modalidade de apoio: | Bolsas no Brasil - Mestrado |