Advanced search
Start date
Betweenand

Assessment of the role of KMT2E in acute myeloid leukemia in the context of all trans retinoic acid

Grant number: 23/11309-4
Support Opportunities:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): January 01, 2024
Effective date (End): December 31, 2024
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Eduardo Magalhães Rego
Grantee:Luíse Araújo de Albuquerque Simões
Supervisor: Jan Jacob Schuringa
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: University Medical Center Groningen (UMCG), Netherlands  
Associated to the scholarship:21/11568-4 - Assessment of the effect of KMT2E expression in Acute Myeloid Leukemia on the response to all trans-retinoic acid (ATRA) and SLIT2 treatment, BP.DD

Abstract

Acute myeloid leukemia (AML) is an aggressive disease with dismal clinical outcome primarily affecting older individuals, frequently unsuitable for intensive chemotherapy. Current, non-intensive chemotherapeutic options, include hypomethylating agents and low-dose of cytarabine, while the differentiation agent all trans retinoic acid (ATRA) has shown success exclusively in acute promyelocytic leukemia (APL) patients. Despite the limited success of ATRA in several AML clinical trials it is possible that only a subgroup of AML patients would benefit from such therapy. Previously our group showed that APL cells with high KMT2E transcript levels are more sensitive to ATRA-driven granulocytic differentiation. In the context of non-APL AML cells, the overexpression of KMT2E led to increased apoptosis in vitro upon ATRA treatment and decreased tumor burden in vivo. In line with our results, western blot analysis showed increased CDKN1A expression in AML cells overexpressing KMT2E when treated with ATRA. Given these results, the overall achieving aim of this research proposal is to study the molecular mechanism via which KMT2E drives increased ATRA response in AML. To do so, we first intend to perform a ChIP-seq and co-IP analysis in AML cell lines overexpressing KMT2E ± ATRA to identify potential DNA binding sites and interaction partners. Next, we will evaluate the response to ATRA in primary patients with different levels of KMT2E in vitro as well as in vivo using the humanized MISTRG mice. Finally, we will perform an RNAseq analysis to capture transcriptional changes that dictate ATRA response in AML cells with high/low KMT2E levels. (AU)

News published in Agência FAPESP Newsletter about the scholarship:
Articles published in other media outlets (0 total):
More itemsLess items
VEICULO: TITULO (DATA)
VEICULO: TITULO (DATA)

Please report errors in scientific publications list using this form.