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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

HUWE1 cooperates with RAS activation to control leukemia cell proliferation and human hematopoietic stem cells differentiation fate

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Author(s):
Ruckert, Mariana Tannus [1, 2] ; Brouwers-Vos, Annet Z. [2] ; Nagano, Luis Fernando P. [1] ; Schuringa, Jan Jacob [2] ; Silveira, Vanessa Silva [1]
Total Authors: 5
Affiliation:
[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
Total Affiliations: 2
Document type: Journal article
Source: Cancer Gene Therapy; v. 27, n. 10-11 JUL 2020.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 15/10694-5 - Dual specificity phosphatases activity on map kinases signaling regulation: impact on pancreatic ductal adenocarcinoma metabolic reprogramming
Grantee:Vanessa da Silva Silveira
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 15/12146-5 - Investigation of ubiquitin-ligase HUWE1 in the modulation of RAS pathway in leukemia models
Grantee:Mariana Tannús Ruckert
Support type: Scholarships in Brazil - Master