[Comparison of Clinical Characteristics of JAK2, CALR and Tri-Negative Driving Mutant Type in Patients with Essential Thrombocythemia].

OBJECTIVE: To investigate the relationship between mutated genes and clinical features in patients with essential thrombocythemia (ET). METHODS: The clinical data of 69 patients with ET from October 2018 to March 2022 were retrospectively analyzed. According to driver mutation type, patients were divided into JAK2 group, CALR group and triple-negative group. The sex, age, cardiovascular risk factors, thrombosis, splenomegaly, routine blood test and coagulation status of patients in three groups were analyzed. RESULTS: Among 69 ET patients, 46 cases were associated with JAK2 mutation, 14 cases with CALR mutation, 8 cases with triple-negative mutation, and one with MPL gene mutation. There were no significant differences in age and sex among the three groups (P >0.05). The highest thrombotic rate was 26.09% (12/46) in JAK2 group, then 12.5% (1/8) in triple-negative group, while no thrombotic events occurred in CALR group. The incidence of splenomegaly was the highest in JAK2 group (34.78%), while no splenomegaly occurred in triple-negative group. The white blood cell (WBC) count in JAK2 group was (9.00±4.86)×109/L, which was significantly higher than (6.03±2.32)×109/L in CALR group (P <0.05). The hemoglobin (Hb) and hematocrit (HCT) in JAK2 group were (148.42±18.79) g/L and (0.44±0.06)%, respectively, which were both significantly higher than (131.00±15.17) g/L and (0.39±0.05)% in triple-negative group (P <0.05). The platelet (PLT) in JAK2 group was (584.17±175.77)×109/L, which was significantly lower than (703.07±225.60)×109/L in CALR group (P <0.05). The fibrinogen (Fg) in JAK2 and triple-negative group were (2.64±0.69) g/L and (3.05±0.77) g/L, respectively, which were both significantly higher than (2.24±0.47) g/L in CALR group (P <0.05, P <0.01). The activated partial thromboplastin time (APTT) in triple-negative group was (28.61±1.99) s, which was significantly decreased compared with (31.45±3.35) s in CALR group (P <0.05). CONCLUSIONS: There are differences in blood cell count and coagulation status among ET patients with different driver gene mutations. Among ET patients, JAK2 mutation is most common. Compared with CALR group, the thrombotic rate, WBC and Fg significantly increase in JAK2 group, while PLT decrease. Compared with triple-negative group, the incidence of splenomegaly and HCT significantly increase. Compared with CALR group, Fg significantly increases but APTT decreases in triple-negative group.

[Possible Risk Factors for Bone Marrow Fibroplasia in Patients with Polycythemia Vera].

OBJECTIVE: To understand the biological characteristics of polycythemia vera (PV) patients with myeloid fibroplasia, and further analyze the risk factors affecting myeloid fibroplasia in PV patients, so as to provide ideas for predicting the occurrence of myeloid fibroplasia in PV patients. METHODS: Forty patients with PV in the Department of Hematology, Xiyuan Hospital of China Academy of Chinese Medical Sciences were collected and divided into two groups, with (hyperplasia group) and without (Non-proliferative group) hyperplasia of bone marrow fibers. The differences of basic clinical characteristics, blood routine, biochemistry, bone marrow cells, coagulation function and other indicators between the two groups were compared, and the independent risk factors affecting the proliferation of bone marrow fibrous tissue in PV patients were further analyzed by multivariate regression. RESULTS: Compared with Non-proliferative group, the JAK2 mutation rate (95% vs 70%，P=0.037), eosinophilic cell count (0.19 vs 0.11, P=0.047) and eosinophilic percentage (1.84 vs 1.27, P=0.001) in PV patients with hyperplasia were significantly increased, triglycerides (1.55 vs 1.91, P=0.038) and low-density lipoprotein (1.50 vs 3.08, P=0.000) were significantly reduced, bone marrow hematopoietic volume (0.85 vs 0.6, P=0.001), granulocyte/erythrocyte ratio (3.40 vs 1.89, P=0.033), lymphocyte/erythrocyte ratio (0.60 vs 0.42, P=0.033), and granulocyte+lymphocyte/erythrocyte ratio (3.72 vs 2.37, P=0.026) were significantly increased, thrombin time (18.84 vs 18.12, P=0.043) was significantly prolonged. Multivariate regression analysis results showed that peripheral blood eosinophil ≥2% and low-density lipoprotein ≤2 mmol/L were independent risk factors for bone marrow fibrous tissue hyperplasia in PV patients (P<0.05). CONCLUSION: Increased proportion of peripheral blood eosinophils and decreased low density lipoprotein are risk factors for bone marrow fibrous tissue hyperplasia in PV patients.

[Analysis of Differential Proteins Related to Platelet Activation in Patients with Essential Thrombocythemia Based on Label-Free Quantitative Technology].

OBJECTIVE: To analysis the specific protein markers of essential thrombocythemia (ET) based on proteomics technology, to explore and verify the differential protein related to platelet activation. METHODS: Blood samples were obtained from ET patients and healthy people and a certain protein mass spectrometry was detected using label-free quantitative technology. The proteins relative abundance increased or down-regulated by 1.3 times in the disease group compared with the control group, and the protein abundance in the two groups t test P＜0.05 were defined as differential proteins. Bioinformatics analysis of the differential proteins was performed using GO and KEGG. The difference in the average protein abundance between the two groups was analyzed by t test and P＜0.05 was considered statistically significant. Differential proteins were selected for verification by parallel reaction monitoring (PRM) technology. RESULTS: A total of 140 differential proteins were found, of which 72 were up-regulated and 68 were down-regulated. KEGG enrichment showed that the differential protein expression was related to the platelet activation pathway. The differential proteins related to platelet activation were GPV, COL1A2, GP1bα, COL1A1 and GPVI. Among them, the expressions of GPV, GP1bα and GPVI were up-regulated, and the expressions of COL1A2 and COL1A1 were down-regulated. PRM verification of COL1A1, GP1bα, GPVI and GPV was consistent with LFP proteomics testing. CONCLUSION: Differential proteins in ET patients are related to platelet activation pathway activation.Differential proteins such as GPV, GPVI, COL1A1 and GP1bα can be used as new targets related to ET platelet activation.

[Analysis of DNA Methylation Gene Mutations and Clinical Features in Patients with Myeloproliferative Neoplasm].

AbstractObjective: To analyze the DNA methylation gene mutations of myeloproliferative neoplasm (MPN), and preliminarily explore its clinical features. METHODS: Next-generation sequencing technology was used to detect 31 MPN-related genes in 105 cases of MPN patients ï¼»40 cases of polycythaemia vera (PV), 65 cases of essential thrombocythemia (ET)ï¼½, and to analyze the relationship between DNA methylation gene mutations and clinical features. RESULTS: 15 mutation types were detected in 105 patients (88 mutations in total), and the total mutation detection rate was 87.6% (92/105). A total of 23 mutations in 4 DNA methylation genes (TET2, DNMT3A, IDH1, IDH2) were detected in 22 patients. The mutation rate of DNA methylation genes was 21.0%, mainly in the form of double mutations, including JAK2 V617F and TET2 (n=10), JAK2 V617F and DNMT3A (n=4), CALR and TET2 (n=2), JAK2 V617F and IDH1 (n=1). Compared with MPN patients without DNA methylation gene mutations, the proportion of women with DNA methylation gene mutations and the white blood cell count (WBC) were significantly higher (P<0.05). Compared with MPN patients with triple-negative driver genes, the proportion of women with DNA methylation gene mutations, age, WBC, platelet count (PLT), and neutrophil-to-lymphocyte ratio (NLR) were significantly higher (P<0.05). The remaining difference was not statistically significant (P>0.05). The MPN10 score, the incidence of thrombotic events, and the proportion of medium-risk and high-risk patients with DNA methylation gene mutations were significantly higher than those of MPN patients without DNA methylation gene mutations (P<0.05). CONCLUSION: The mutation rate of DNA methylation genes was 21.0%, mainly coexisting in the form of double mutations. The proportion of women with DNA methylation gene mutations in MPN patients and WBC is high, the symptom load is heavy, the incidence of thrombosis is high, and the proportion of medium-high-risk patients is high, suggesting that their prognosis may be poor.