Study On Gene JAK2and ASXL1Mutations In Polycythemia Vera

ObjectiveTo study the relationship between the genes in signaling pathways orepigenetic regulators (JAK2V617F，JAK2V617F mutation burden，JAK2exon12，ASXL1，MPL，SETbp1and IDH1/2) and the polycythemia vera(PV).MethodsA retrospective study was performed on135PV cases according to theWorld Health Organization (WHO) diagnostic criteria of2008.Identification ofthe JAK2V617F gene mutation was detected by nested alleles polymerasechain reaction,then for the JAK2V617F mutation positive patients，JAK2V617Fmutation burden was detected by real-time quantitative polymerase chainreaction (RQ-PCR) using Taqman-MGB probe.And identification of the othersgene (ASXL1exon12,MPL enxon10,SETbp1exon4,IDH1/2exon4) wasdetected by Sanger sequencing.The clinical and laboratory features werecompared in patients between gene mutation and the wild type.ResultsASXL1、IDH1、IDH2were mutated in7.69%（8/104）、0.08%(1/120)、and0.08%(1/121).JAK2was mutated in82.22%(111/135), among them, themutation rate of JAK2exon12was2.96%(4/135).However, there was nomutation of MPLW515and SETBP1in these PV patients. The mutation ofASXL1was31.82%（7/22）in PPMF patients. Gene mutation in ASXL1isgiven priority to with frameshift mutation, in addition to including missense mutation and nonsense mutation.The result showed that ASXL1is correlated with JAKV617F allele burden(rs=-0.298，P=0.002) by Spearman rank correlation. The hemoglobin waslower in patients with ASXL1mutation. The result of Kaplan-Meier survivalanalysis showed that ASXL1mutation (Log Rank=9.189, P=0.002),JAKV617F allele burden higher than50%(Log Rank=9.339,P=0.002) andleukocyte count≥25×109/L(Log Rank=4.191,P=0.041) were the risk factorsfor survival of no PPMF. ASXL1mutation(β=3.47，Wald=3.932，OR=32.151，P=0.047，95%CI=1.041-992.968), JAKV617F allele burden higher than50%（β=-1.582，Wald=5.157，OR=0.206，P=0.023，95%CI=0.052-0.805) andsplenomegaly (β=3.292，Wald=8.565，OR=26.898，P=0.003，95%CI=2.967-243.892) were the risk-factors of PPMF by multiple-factor analysis of Logistic.Conclusions1. The mutation frequency of JAK2and ASXL1gene in Chinese PV patientswas consistent with that of western country.And the gene mutation wererare in the IDH1, IDH2, SEPTBP1and MPL.2. The ASXL1mutation was correlation with JAKV617F allele burden.3. The ASXL1mutation，higher JAK2V617F allele burden andsplenomegaly maybe the risk-factors of PPMF.