Molecular landscape of the JAK2 gene in chronic myeloproliferative neoplasm patients from the state of Amazonas, Brazil

Dania G Torres; Emanuela V Barbosa Alves; Miliane Araújo de Sousa; Wanessa H Laranjeira; Jhemerson Paes; Erycka Alves; Deborah Canté; Allyson G Costa; Adriana Malheiro; Rosângela Abreu; Leny Nascimento; Nelson A Fraiji; George A V Silva; Lucivana P de Souza Mourão; Andréa M Tarragô

doi:10.3892/br.2023.1680

Molecular landscape of the JAK2 gene in chronic myeloproliferative neoplasm patients from the state of Amazonas, Brazil

Biomed Rep. 2023 Oct 23;19(6):98. doi: 10.3892/br.2023.1680. eCollection 2023 Dec.

Authors

Dania G Torres^{1

2

3}, Emanuela V Barbosa Alves^{1

2}, Miliane Araújo de Sousa^{1

2}, Wanessa H Laranjeira^{1

2}, Jhemerson Paes^{1

2}, Erycka Alves^{1

2}, Deborah Canté^{1

2}, Allyson G Costa^{1

2

4

5

6}, Adriana Malheiro^{1

2

4

6}, Rosângela Abreu^{1

2}, Leny Nascimento^{1

2}, Nelson A Fraiji^{1

2}, George A V Silva^{1

6

7}, Lucivana P de Souza Mourão^{1

8}, Andréa M Tarragô^{1

2

4

6}

Affiliations

¹ Post-graduate Program in Sciences Applied to Hematology, University of Amazonas State, Manaus, Amazonas State 69850-001, Brazil.
² Board of Teaching and Research, Hospital Foundation for Hematology and Hemotherapy of Amazonas, Manaus, Amazonas State 69050-001, Brazil.
³ Molecular Biology Center, University of Central America, Managua 14003, Nicaragua.
⁴ Post-graduate Program in Basic and Applied Immunology, Federal University of Amazonas, Manaus, Amazonas State 69067-005, Brazil.
⁵ Manaus School of Nursing, Federal University of Amazonas, Manaus, Amazonas State 69057-070, Brazil.
⁶ Amazon Genomic Health Surveillance Network Coordination, Manaus, Amazonas State 69040-010, Brazil.
⁷ Leonidas and Maria Deane Institute, Oswaldo Cruz Foundation, Manaus, Amazonas State 69027-070, Brazil.
⁸ Superior School of Health Sciences, Amazonas State University, Manaus, Amazonas State 69065-001, Brazil.

Abstract

JAK2V617F (dbSNP: rs77375493) is the most frequent and most-studied variant in BCR::ABL1 negative myeloproliferative neoplasms and in the JAK2 gene. The present study aimed to molecularly characterize variants in the complete coding region of the JAK2 gene in patients with BCR::ABL1 negative chronic myeloproliferative neoplasms. The study included 97 patients with BCR::ABL1 negative myeloproliferative neoplasms, including polycythemia vera (n=38), essential thrombocythemia (n=55), and myelofibrosis (n=04). Molecular evaluation was performed using conventional PCR and Sanger sequencing to detect variants in the complete coding region of the JAK2 gene. The presence of missense variants in the JAK2 gene including rs907414891, rs2230723, rs77375493 (JAK2V617F), and rs41316003 were identified. The coexistence of variants was detected in polycythemia vera and essential thrombocythemia. Thus, individuals with high JAK2V617F variant allele frequency (≥50% VAF) presented more thrombo-hemorrhagic events and manifestations of splenomegaly compared with those with low JAK2V617F variant allele frequency (<50% VAF). In conclusion, individuals with BCR::ABL1 negative neoplasms can display >1 variant in the JAK2 gene, especially rs2230722, rs2230724, and rs77375493 variants, and those with high JAK2V617F VAF show alterations in the clinical-laboratory profile compared with those with low JAK2V617F VAF.

Keywords: JAK2; chronic myeloproliferative neoplasms; coding region; sanger sequencing; variant allele frequency.

Grants and funding

Funding: The present study was supported by the Fundação de Amparo à Pesquisa do Estado do Amazonas (Pro-Estado Program; grant nos. #002/2008, #007/2018 and #005/2019, and POSGRAD Program grant nos. #008/2021), Conselho Nacional de Desenvolvimento Científico e Tecnológico, and Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior.