Clinical Characteristics Of 73 Cases Of BCR-ABL Negative Myeloproliferative Neoplasms

Objective: To retrospectively analyze the clinical data of 73 patients with BCR-ABL fusion gene negative myeloproliferative neoplasms(MPN).To observe the occurrence of thrombosis,hemorrhage and splenomegaly in MPN patients and the relationship between JAK2,MPL and CALR mutation genes and clinical features,so as to provide evidence for the diagnosis and treatment of MPN.Methods: 73 MPN patients diagnosed in Hematology Department of Hebei People's Hospital from January 2016 to December 2018 were selected.All patients were negative for BCR-ABL fusion gene.The diagnosis of PV,ET and PMF were according to WHO diagnostic criteria in 2016.General data(gender,age at first diagnosis),clinical manifestations(thrombosis,hemorrhage,splenomegaly) and related laboratory examinations(blood routine,driver gene mutation) were analyzed.All data were analyzed by SPSS 21.0 software,P<0.05 was statistical significance.Result: 1 General characteristics of MPN patients:There were 28 patients with PV(38.36%),33 patients with ET(45.20%),and 12 patients with PMF(16.44%).Male to female ratio: 1.43:1.The median age of the initial diagnosis was 64 years(23-87 years).2 The expression of driver gene mutations in MPN patients: 2.1 In 73 patients with MPN,the total mutation rate of JAK2V617F,CALR or MPL gene was 87.7%.Among them,the total mutation rate of JAK2V617F was 74%,the total mutation rate of CALR was 12.3%,the mutation rate of type I was 5.48%,the mutation rate of type II was 6.85%,the total mutation rate of MPL was 1.4%,and the mutation rate of triple negative myeloproliferative neoplasms(TN MPN)was 12.3%.2.2 In PV patients,the mutation rate of JAK2V617F was 89%,and the triple negative patients was 11%.In ET patients,the mutation rate of JAK2V617F was 70%,the mutation rate of CALR was 18.2%,and the triple negative patients was 11.8%.In PMF patients,the mutation rate of JAK2V617F was 50%,the mutation rate of CALR was 25%,the mutation rate of MPL was 8.3%,and the mutation rate of triple negative patients was 16.7%.The incidence of JAK2V617F mutation in PV patients was higher than that in PMF patients(P=0.012),while the incidence of CALR mutation was lower than that in PMF patients(P=0.022).3 The incidence of thrombosis,hemorrhage,and splenomegaly:Among the PV patients,20 cases had thrombosis(71.43%),3 cases had hemorrhage(10.71%),and 10 cases had splenomegaly(35.71%).Among the ET patients,15 cases had thrombosis(45.46%),7 cases had hemorrhage(21.21%),and 3 cases had splenomegaly(9.09%).Among the PMF patients,9 cases had splenomegaly(75.0%),and no thrombosis or hemorrhage was found.The incidence of thrombosis of PV patients was higher than that of PMF patients(P<0.0001);The incidence of thrombosis of ET patients was higher than that of PMF patients(P=0.0004).The incidence of splenomegaly of PV patients was higher than that of ET patients(P=0.011);The incidence of splenomegaly of ET patients was lower than that of PMF patients(P<0.0001).4 Correlation between driver genes mutation and clinical features of MPN patients: 4.1 In patients with PV,age,white blood cell count,hemoglobin level,and platelet count of patients with positive JAK2V617F mutation were significantly higher than those of triple-negative patients(P<0.05).4.2 In patients with ET,age and white blood cell count of patients with positive JAK2V617F mutation were significantly higher than those with positive CALR mutations,while the platelet count was significantly lower than that of patients with positive CALR mutations(P<0.05).The platelet count of patients with triple negative was significantly higher than that of patients with positive JAK2V617F mutation(P<0.05).5 Gene mutation expression by NGS detection in patients with TN MPN:9 patients with TN MPN included 3 patients with PV,4 patients with ET,and 2 patients with PMF.NGS examination showed JAK2 exon12,non-"hot spot" CALR,epigenetic related genes(ASXL1,IDH2,DNMT3 A and TET2),transcription factor(RUNX1) and splice gene(SRSF2) mutations.No mutations were detected in 2 patients with ET.6 Clinical features of TN MPNpatients:Among 9 patients with TN MPN,the hemoglobin content of PV patients was higher.ET patients had younger onset age and higher platelet count.The hemoglobin content of PMF patients was lower.Conclusion:1.The positive rate of driving gene mutation is different in MPN patients,which plays an assistant role in differential diagnosis of different diseases.2.The incidence of thrombosis in PV and ET patients was higher than that in PMF patients;the incidence of splenomegaly in PV and PMF patients was higher than that in ET patients.3.The positive rates of the three driver gene mutations varied in the clinical phenotype and blood profile of patients with different MPN.4.The gene mutation of TN MPN patients showed diversity.The pathogenesis may have relationship with the non-"hot spot" mutation of drier genes and other mutations related to myeloid tumors.