The Diagnostic Significance Of JAK2,CALR And MPL Mutations In BCR-ABL Negative Myeloproliferative Neoplasms

Background Myeloproliferative neoplasms(MPNs)are clonal hematopoietic stem cell diseases characterized by proliferation of one or more myeloid lineages in the bone marrow.MPNs have a high morbidity rate which is proved by epidemiological investigation and the morbidity is on rise year by year.So,it is important to diagnose and treat these diseases.Ph chromosome or BCR-ABL fusion gene is a specific marker for CML,it is of great significance in diagnosis,and follow-up assessment of treatment effect for CML patients.Tyrosine Kinase Inhibitor,which is the gene derivative,has been the first-line drugs to treat CML.The etiology and pathogenesis of CML has been relatively clear due to the discovery of BCR-ABL gene,the pathogenesis of the other BCR-ABL negative MPN is not yet very clear.Therefore,it is important to find kinds of molecular markers which have a sharp specificity and a high sensibility,just like BCR-ABL fusion gene.JAK2 V617 F is not to be found until 2005.And it was widely recognized to be the most meaningful mutant gene after BCR-ABL fusion gene.This has lead to substantive gains in the understanding of the pathogenesis of BCR-ABL negative MPNs.But JAK2 V617 F mutation can’t explain the mechanism of development of PV,ET and PMF completely.In addition,JAK2 exon 12,MPL515 and CALR gene mutations have been discovered and these markers have been found to be helpful to understand the molecular pathogenesis of MPN,but also contribute to the diagnosis and treatment of these diseases.These kinds of mutations activate the signaling pathway of JAK-STAT and are the driver mutation of the MPNs of negative BCR-ABL.To explore the diagnostic value of JAK2,CALR and MPL mutations in BCR-ABL negative MPNs.The positive rates of JAK2,CALR and MPL mutations in 171 patients were compared.In addition,the sensitivity,specificity,positive predictive value,negative predictive value and coincidence rate of mutation detection were analyzed for the diagnosis of BCR-ABL negative MPNs.Objective To investigate the diagnostic value of JAK2,CALR and MPL mutations in BCR-ABL negative myeloproliferative neoplasms(MPNs).Methods A total of 171 patients with MPNs were analyzed retrospectively,including 110 BCR-ABL negative MPN patients were enrolled as the case group,65 patients non BCR-ABL nemgative MPNs were enrolled as the control group.The sensitivity,specificity,positive predictive value,negative predictive value and coincidence rate of mutation detection were analyzed for the diagnosis of BCR-ABL negative MPNs.Results 1.Compared with the control group,the positive rate of JAK2,CALR and MPL mutation were significantly increased(P<0.01);The sensitivity,negative predictivevalue and coincidence rate of the combined detection were increased to 84.9%,79.2%,and 88.3 %,respectively.(specificity rate:93.9;kappa:k=0.76).2.Select the classic BCR-ABL negative myeloproliferative neoplasm(MPN)patients as the object.With WHO diagnosis standard as the reference,the coincidence rates of single gene mutation or bone marrow pathological diagnosis were 85.1% and 90.1% respectively,and there was no significant difference between the two methods(P>0.05).The coincidence rate between gene detection and bone marrow pathology was 75.2%(P>0.05).Conclusion 1.The combination of JAK2,CALR and MPL mutation will remarkably increase the sensitivity and coincidencerate of diagnosis on BCR-ABL negative MPNs,and will relatively maintain a high specificity.2.There is a high consistency between mutation detection and bone marrow pathological for diagnosing the classic BCR-ABL negative MPN.