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

Exploring hematological alterations and genetics linked to SNV rs10974944 in myeloproliferative neoplasms among Amazon patients

“…Essential thrombocythemia proved to be the most frequent myeloproliferative neoplasm, which are findings that align with the premises established by Torres 15 , who studied a population with BCR::ABL1 -negative myeloproliferative neoplasms in the state of Amazonas (Brazil). Similar data were described by Macedo 16 , who reported a similar scenario in patients from the states of Paraná and São Paulo who had the same hematologic malignancy, and these data converge with descriptions found in other countries 17 , 18 .…”

“…The variant was identified according to the parameters and specifications established by Torres et al 15 . The negative status for the JAK2 V617F variant was confirmed using the allele-specific PCR technique.…”

Hematological alterations associated with the SNV rs10974944, part of the 46/1 haplotype, in patients from the Brazilian Amazon with BCR::ABL1-negative myeloproliferative neoplasms

“…Essential thrombocythemia proved to be the most frequent myeloproliferative neoplasm, which are ndings that align with the premises established by Torres 15 , who studied a population with BCR::ABL1-negative myeloproliferative neoplasms in the state of Amazonas (Brazil). Similar data were described by Macedo 16 , who reported a similar scenario in patients from the states of Paraná and São Paulo who had the same hematologic malignancy, and these data converge with descriptions found in other countries 17,18 The age range of individuals was between the fth and seventh decades of life, which is consistent with what is stated in other studies 19,20 .…”