Influence of Genetic Variations in miRNA and Genes Encoding Proteins in the miRNA Synthesis Complex on Toxicity of the Treatment of Pediatric B-Cell ALL in the Brazilian Amazon

Elisa da Silva Menezes; Francisco Cezar Aquino de Moraes; Amanda de Nazaré Cohen-Paes; Alayde Vieira Wanderley; Esdras Edgar Batista Pereira; Lucas Favacho Pastana; Antônio André Conde Modesto; Paulo Pimentel de Assumpção; Rommel Mario Rodríguez Burbano; Sidney Emanuel Batista Dos Santos; Ney Pereira Carneiro Dos Santos; Marianne Rodrigues Fernandes

doi:10.3390/ijms24054431

Influence of Genetic Variations in miRNA and Genes Encoding Proteins in the miRNA Synthesis Complex on Toxicity of the Treatment of Pediatric B-Cell ALL in the Brazilian Amazon

Int J Mol Sci. 2023 Feb 23;24(5):4431. doi: 10.3390/ijms24054431.

Authors

Elisa da Silva Menezes¹, Francisco Cezar Aquino de Moraes¹, Amanda de Nazaré Cohen-Paes¹, Alayde Vieira Wanderley^{2

3}, Esdras Edgar Batista Pereira^{1

3

4

5}, Lucas Favacho Pastana¹, Antônio André Conde Modesto¹, Paulo Pimentel de Assumpção¹, Rommel Mario Rodríguez Burbano^{1

6}, Sidney Emanuel Batista Dos Santos^{1

4}, Ney Pereira Carneiro Dos Santos¹, Marianne Rodrigues Fernandes¹

Affiliations

¹ Oncology Research Center, Federal University of Pará, Belém 66073-005, PA, Brazil.
² Otávio Lobo Children's Cancer Hospital, Belém 66063-005, PA, Brazil.
³ State Department of Public Health (SESPA), Belém 66093-677, PA, Brazil.
⁴ Laboratory of Human and Medical Genetics, Institute of Biological Science, Federal University of Pará, Belém 66077-830, PA, Brazil.
⁵ Instituto Tocantinense Presidente Antônio Carlos (ITPAC), Abaetetuba 68440-000, PA, Brazil.
⁶ Ophir Loyola Hospital, Molecular Biology Laboratory, Belém 66063-240, PA, Brazil.

Abstract

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer in the world. Single nucleotide variants (SNVs) in miRNA and genes encoding proteins of the miRNA synthesis complex (SC) may affect the processing of drugs used in the treatment of ALL, resulting in treatment-related toxicities (TRTs). We investigated the role of 25 SNVs in microRNA genes and genes encoding proteins of the miRNA SC, in 77 patients treated for ALL-B from the Brazilian Amazon. The 25 SNVs were investigated using the TaqMan^® OpenArray™ Genotyping System. SNVs rs2292832 (MIR149), rs2043556 (MIR605), and rs10505168 (MIR2053) were associated with an increased risk of developing Neurological Toxicity, while rs2505901 (MIR938) was associated with protection from this toxicity. MIR2053 (rs10505168) and MIR323B (rs56103835) were associated with protection from gastrointestinal toxicity, while DROSHA (rs639174) increased the risk of development. The rs2043556 (MIR605) variant was related to protection from infectious toxicity. SNVs rs12904 (MIR200C), rs3746444 (MIR499A), and rs10739971 (MIRLET7A1) were associated with a lower risk for severe hematologic toxicity during ALL treatment. These findings reveal the potential for the use of these genetic variants to understand the development of toxicities related to the treatment of ALL in patients from the Brazilian Amazon region.

Keywords: SNVs; acute lymphoblastic leukemia; ancestry; miRNA; toxicity.

MeSH terms

Brazil
Child
Humans
MicroRNAs* / genetics
Polymorphism, Single Nucleotide
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma*
Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics

Substances

MicroRNAs
MIRN149 microRNA, human
MIRN605 microRNA, human

Grants and funding

Coordenação de Aperfeiçoamento de Pessoal e Nível Superior (CAPES); Fundação Amazônia de Amparo a Estudos e Pesquisas (FAPESPA); and Universidade Federal do Pará (UFPA).