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.
