The Expressions And Clinical Significance Of JAK2V617F Mutation In The Patients With Myeloproliferative Disorders

Objective Myeloproliferative disorder(MPD)is one of malignant clonal hematopoietic stem/progenitor cell disorders.The classical BCR/ABL negative MPDs mainly include polycythemia vera(PV),essential thrombocythemia(ET),idiopathic myelofibrosis(IMF)and chronic myeloid leukemia(CML).Except for CML with Ph chromosome and BCR/ABL fusion gene,the pathogenesis of other MPDs' molecular remain unclear.In recent years,JAK2V617F,a gain of function mutation,has been detected in approximate 90%of PV and half of ET and IMF patients.JAK2 is a constitutive protein tyrosine kinase(PTK)which can activate JAK-STAT signaling. JAK2V617F point mutation can change tyrosine kniase JAK2 space conformation and make it activated without cytokines and stimulate hematopoietic cells proliferating persistently.This study is to detect the expressions of JAK2V617F in MPDs,benign and other malignant hematological diseases and healthy people. Analyze the difference of the clinical manifestations,lab findings and therapeutic efficacy between JAK2V617F positive and JAK2V617F negative MPD patients.Methods.The peripheral blood or bone marrow samples were obtained after informed consent from 64 MPDs patients(22 PV cases,14 IMF cases,12 ET cases, 12 CML cases,3 CMML cases and 1 MPD-u case)and 15 non-myeloproliferative disorder cases(5 immune related pancytopenia cases,5 NHL cases and 5 AML cases) and 5 healthy people cases as control.The JAK2V617F mutation was detected by reverse-transcription polymerase chain reaction(RT-PCR)method.The results were analyzed by t test,chi-square test and Spearman correlate analysis.Results The JAK2V617F point mutation was detected in 64 MPDs patients,including 19/22(86.36%)PV patients,8/14(57.14%)IMF patients,5/12(41.67%)ET patients. There were no JAK2V617F point mutation detected in CML,CMML,MPD-u and 20 control cases.The mutation rate in BCR/ABL negative MPDs(50%)was significantly higher than that in CML(0%)and control(0%)(P＜0.05).The comparison of clinical characteristics:①The JAK2V617F mutation was detected in 32 BCR/ABL negative MPD patients,including 19/22(86.36%)PV patients,5/12(41.67%)ET patients and 8/14(57.14%)IMF patients.The mutation was not detected in CML,CMML,MPD-u and other controls.The mutation rate in BCR/ABL negative MPDs(61.52%)was significantly higher than that in CML and controls.Comparing the PV,ET and IMF, we found that the mutation rate in PV was much higher than that in ET (x~2=2.693,P=0.007)rather than in IMF(x~2=1.946,P=0.052).There was no statistically significant difference in mutation rate between ET and IMF(P=0.440).②The peripheral hemoglobin and platelet level in JAK2V617F positive mutation PV patients were statistically significant higher than that in JAK2V617F negative patients. In PV patients there was a positive correlation between the expression of JAK2V617F mutation and the level of hemoglobin and platelet(P＜0.05).Compared with the JAK2V617F negative PV patients,the mutation positive patients had no statistically significant difference(P＜0.05),but there was a negative correlation between the level of EPO and the expression of JAK2 mutation(r=-0.588,P=0.008).In IMF patients, the hemoglobin level was statistically significant higher in mutation positive group than that in negative group(P＜0.05).③There were no statistical differences in the percentage of erythrocytic lineage,the degree of splenomegaly and thrombosis was between mutation positive and negative subgroup of PV,ET and IMF.④The expression of JAK2V617F mutation has no relationship with the abnormal chromosome in BCR/ABL negative MPDs.⑤Twenty-one patients(PV 11 cases,ET 3 cases and IMF 7cases)were followed up and were found that there was no significant difference in therapeutic efficacy between the mutation negative group and positive group.Conclusion JAK2V617F point mutation was detected in a sizeable proportion of three subgroups' classical BCR/ABL negative MPD patients,especially in PV patients.In our study,we didn't detect any JAK2V617F mutation in other benign and malignant hematological diseases and healthy people.Maybe we can conclude that the JAK2V617F mutation contribute to the genesis of BCR/ABL negative MPDs. Compared with the mutation negative group,the mutation positive PV patients had significant higher hemoglobin concentration and platelet counts as well as lower EPO level.The IMF mutation positive group had statistically significant higher hemoglobin level than the negative group.Now the JAK2V617F mutation has become an important molecular marker in MPD's diagnosis and classification. Detecting the mutation may be helpful for diagnosis and treatment of MPD.