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Clonal hematopoiesis in patients with telomeric dysfunction

Grant number: 17/09428-4
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): August 01, 2017
Effective date (End): October 31, 2021
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Rodrigo do Tocantins Calado de Saloma Rodrigues
Grantee:Flávia Sacilotto Donaires Ramos
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:13/08135-2 - CTC - Center for Cell-Based Therapy, AP.CEPID


Hematopoietic stem cells may acquire mutations that confer a replicative advantage, leading to the expansion of the mutated cell, the so-called clonal hematopoiesis. Somatic mutations that give rise to clonal hematopoiesis are rare in the first four decades of life but increase in frequency with aging, affecting mainly three genes: DNMT3A, TET2 e ASXL1. These genes are also frequently mutated in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Thus, the clonal hematopoiesis may be an indicative of the pre-malignant state. Patients with telomere dysfunction affecting the hematopoietic compartment may present clonal evolution and MDS/AML. In this context, we hypothesized whether clonal hematopoiesis might occur more frequently in patients with telomere dysfunction, compared to the population not presenting this dysfunction. Here, we plan to investigate somatic mutations in peripheral blood cells from patients with telomere dysfunction (either germline mutations in telomere biology genes or critically short telomeres). We will perform next generation sequencing to detect the somatic mutations in a panel of 54 genes related to myeloid neoplasms. We will also assess the possible risk factors associated with somatic mutations, such as germline mutation, telomere length, and patient's treatment. These results may provide new insights for detecting pre-malignancy in patients with telomere dysfunction.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GUTIERREZ-RODRIGUES, FERNANDA; MUNGER, ERIC; MA, XIAOYANG; GROARKE, EMMA M.; TANG, YOUBAO; PATEL, BHAVISHA A.; CATTO, LUIZ FERNANDO B.; V. CLE, DIEGO; NIEWISCH, MARENA R.; ALVES-PAIVA, RAQUEL M.; et al. Differential diagnosis of bone marrow failure syndromes guided by machine learning. Blood, v. 141, n. 17, p. 14-pg., . (16/12799-1, 13/08135-2, 17/09428-4, 14/26379-9, 16/03620-8)
PEDRO HENRIQUE PADILHA; GUSTAVO BORGES; BARBARA AMÉLIA SANTANA; LARISSA ALESSANDRA MEDEIROS; SAMIR KANAAN NABHAN; RICARDO PASQUINI; FLAVIA SACILOTTO DONAIRES; RODRIGO TOCANTINS CALADO. THPO gene variants in patients with acquired aplastic anemia. Hematology, Transfusion and Cell Therapy, v. 40, n. 4, p. 339-342, . (17/09428-4, 13/08135-2)
CATTO, LUIZ FERNANDO B.; BORGES, GUSTAVO; PINTO, ANDRE L.; CLE, DIEGO V.; CHAHUD, FERNANDO; SANTANA, BARBARA A.; DONAIRES, FLAVIA S.; CALADO, RODRIGO T.. Somatic genetic rescue in hematopoietic cells in GATA2 deficiency. Blood, v. 136, n. 8, p. 1002-1005, . (14/26379-9, 13/08135-2, 17/09428-4)

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