[Effect of ten-eleven translocation methylcytosine dioxygenase 2 gene mutations on the secondary myelofibrosis of JAK2V617F positive myeloproliferative neoplasms patients].

Objective: To investigate the effect of ten-eleven translocation methylcytosine dioxygenase 2 (TET2) gene mutations on the secondary myelofibrosis (SMF) of JAK2^V617F+ myeloproliferative neoplasms (MPN) patients. Method: A retrospective collection was conducted on MPN patients with JAK2^V617F mutation detected by second-generation sequencing in the Department of Hematology, the Second Hospital of Tianjin Medical University. TET2⁺JAK2^V617F+ MPN patients were selected as the mutant group, and TET2^-JAK2^V617F+ MPN patients matched for age and gender were selected as the non-mutant group. The differences in mortality and SMF between the two groups were followed up until November 11, 2022. The second-generation sequencing technology was used to detect 325 mutated genes in hematological malignancies, in order to determine the differences between two groups of mutated genes. Enzyme linked immunosorbent assay (ELISA) was used to detect and compare the levels of cytokines such as transforming growth factor (TGF)-β1, interleukin (IL)-17, interferon (IFN)-γ in the bone marrow supernatant of the both groups. Multivariate Cox regression analysis was used to investigate the influencing factors of SMF in JAK2^V617F+ MPN patients. Result: A total of 96 patients were included, with 32 in the mutant group, including 16 males and 16 females, aged [M (Q₁, Q₃)] 61 (53, 70) years, and 64 in the non-mutant group, including 32 males and 32 females, aged 58 (51, 68) years. After a follow-up of 61(43, 116) months, the mortality rate of patients in the mutant group [15.6% (5/32) vs 1.6% (1/64), P=0.007] and the proportion of SMF [43.8% (14/32) vs 14.1% (9/64), P=0.001] were higher than those in the non-mutant group. The proportion of FAT1 [25.0% (8/32) vs 7.8% (5/64), P=0.028], U2AF1 [15.6% (5/32) vs 0, P=0.003], and KMT2D [15.6% (5/32) vs 3.1% (2/64), P=0.039] gene mutations in the mutant group was higher than that in the non-mutant group. The mutant group had higher levels of TGF-β1 [13 837(8 298, 17 509) vs 7 915 (3 586, 10 545) ng/L, P=0.016], IL-17 [7.4 (6.3, 7.5) vs 6.1 (5.9, 7.1) ng/L, P=0.007], and IFN-γ[8.5 (8.1, 9.1) vs 8.0 (7.5, 8.3) ng/L, P=0.007] compared to the non-mutant group. The results of multivariate Cox regression analysis showed that TET2 mutation (HR=8.483, 95%CI: 1.278-56.330) was a risk factor of SMF in JAK2^V617F+ MPN patients. Conclusion: TET2 mutation is a risk factor for SMF in JAK2^V617F+ MPN patients.