<abstract xmlns="http://www.w3.org/1999/xhtml"><bold>Background</bold>: Pathogenesis and phenotypic diversity in myeloproliferative neoplasms (MPN) cannot be fully explained by the currently known acquired mutations alone. Some susceptible germline variants of different genes have been proved to be associated with the development of these diseases. The goal of our study was to evaluate the association between the rs3184504 polymorphism of SH2B3 (LNK) gene (p.R262W, c.784T>C) and the risk of developing the four typical MPN - polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), and chronic myeloid leukemia (CML).<bold>Material and methods</bold>: We investigated the SH2B3 rs3184504 T>C polymorphism by real-time PCR in 1901 MPN patients (575 with PV, 798 with ET, 251 with PMF, and 277 with CML), all of them harboring one of the specific driver mutations - JAK2 V617F or CALR in case of PV, ET and PMF, or BCR-ABL1 in case of CML, and 359 controls.<bold>Results</bold>: Overall, the TT homozygous genotype was significantly associated with BCR-ABL1-negative MPN (OR = 1.34; 95% CI = 1.03-1.74; crude p-value = 0.02; adjusted p-value = 0.04). The most significant association was seen in case of PV (OR = 1.54; 95% CI = 1.14-2.06; crude p-value = 0.004; adjusted p-value = 0.024). Also, SH2B3 rs3184504 correlated significantly with JAK2 V617F-positive MPN (OR = 1.36; 95% CI = 1.04-1.77; crude p-value = 0.02; adjusted p-value = 0.08), but not with those CALR-positive. ET (regardless of molecular subtype) and CML were not correlated with SH2B3 rs3184504.<bold>Conclusions</bold>: The SH2B3 rs3184504 polymorphism is associated with risk of MPN development, especially PV. This effect is restricted to JAK2 V617F-positive PV and PMF only.</abstract>

Background: Pathogenesis and phenotypic diversity in myeloproliferative neoplasms (MPN) cannot be fully explained by the currently known acquired mutations alone. Some susceptible germline variants of different genes have been proved to be associated with the development of these diseases. The goal of our study was to evaluate the association between the rs3184504 polymorphism of SH2B3 (LNK) gene (p.R262W, c.784T>C) and the risk of developing the four typical MPN - polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), and chronic myeloid leukemia (CML).Material and methods: We investigated the SH2B3 rs3184504 T>C polymorphism by real-time PCR in 1901 MPN patients (575 with PV, 798 with ET, 251 with PMF, and 277 with CML), all of them harboring one of the specific driver mutations - JAK2 V617F or CALR in case of PV, ET and PMF, or BCR-ABL1 in case of CML, and 359 controls.Results: Overall, the TT homozygous genotype was significantly associated with BCR-ABL1-negative MPN (OR = 1.34; 95% CI = 1.03-1.74; crude p-value = 0.02; adjusted p-value = 0.04). The most significant association was seen in case of PV (OR = 1.54; 95% CI = 1.14-2.06; crude p-value = 0.004; adjusted p-value = 0.024). Also, SH2B3 rs3184504 correlated significantly with JAK2 V617F-positive MPN (OR = 1.36; 95% CI = 1.04-1.77; crude p-value = 0.02; adjusted p-value = 0.08), but not with those CALR-positive. ET (regardless of molecular subtype) and CML were not correlated with SH2B3 rs3184504.Conclusions: The SH2B3 rs3184504 polymorphism is associated with risk of MPN development, especially PV. This effect is restricted to JAK2 V617F-positive PV and PMF only.

<italic>SH2B3 (LNK)</italic> rs3184504 polymorphism is correlated with <italic>JAK2</italic> V617F-positive myeloproliferative neoplasms

“Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca

George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures

“Victor Babes” University of Medicine and Pharmacy

“Iuliu Hatieganu” University of Medicine and Pharmacy and “Ion Chiricuta” Cancer Institute

Department of Pharmacology and Toxicology

“Iuliu Hatieganu” University of Medicine and Pharmacy

Revista Romana de Medicina de Laborator

This work is licensed under the Creative Commons Attribution 4.0 Public License.

 rs3184504 polymorphism is correlated with  V617F-positive myeloproliferative neoplasms

Background: Pathogenesis and phenotypic diversity in myeloproliferative neoplasms (MPN) cannot be fully explained by the currently known acquired mutations...

SH2B3 (LNK) rs3184504 polymorphism is correlated with JAK2 V617F-positive myeloproliferative neoplasms

Publicado en línea: 27 jul 2020

Páginas: 267 - 277

Recibido: 15 feb 2020

Aceptado: 05 abr 2020

DOI: https://doi.org/10.2478/rrlm-2020-0025

Palabras clave
myeloproliferative neoplasms, somatic mutations, genetic predisposition

© 2020 Adrian P. Trifa et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 Public License.

SH2B3 (LNK) rs3184504 polymorphism is correlated with JAK2 V617F-positive myeloproliferative neoplasms

Publicado en línea: 27 jul 2020

Páginas: 267 - 277

Recibido: 15 feb 2020

Aceptado: 05 abr 2020

DOI: https://doi.org/10.2478/rrlm-2020-0025

Palabras clavemyeloproliferative neoplasms, somatic mutations, genetic predisposition

© 2020 Adrian P. Trifa et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 Public License.

Palabras clave
myeloproliferative neoplasms, somatic mutations, genetic predisposition