Analysis of JAK2V617F and MPLW515L/K Mutation in 30 Patients with Early Stage Myeloproliferative Disease

Abstract

The classic Bcr-Abl negative myeloproliferative disorders (MPDs) comprise polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (IMF). They are considered clonal stem cell disorders. Recently two acquired somatic mutations JAK2V617F and MPLW515L/K have been identified to play an important role in pathogenisis of MPDs. JAK2V617F was detected in almost all PV and nearly 50% in ET and IMF, and the MPLW515L/K mutation occured in only 1% and 4% in ET and IMF respectively. However it is interesting that there are some patients with slightly increased blood cells did not meet the criteria of PV and ET clinically. These early prefibrotic stages of MPDs are overlooked by both the Polycythemia Vera Study Group (PVSG) and the 2001 WHO criteria for the diagnosis of PV, ET and IMF. In order to investigate the prevalence of JAK2V617F and MPLW515L/K mutation in patients with early MPDs without a secondary cause, genomic DNA from bone marrow or blood mononuclear cells of 30 patients with early MPDs was screened by allele specific polymerase chain reaction (AS-PCR) for JAK2V617F and MPLW515L/K mutations and the history of thrombosis was assessed retrospectively by using patient files. Results showed that 14 out of 30 patients (46.7%) were positive for the JAK2V617F mutation, and none of them had the MPLW515L/K. Of the 14 patients with JAK2V617F mutation, a history of thrombosis was comfirmed in 5 patients(35.7%), while none of 16 patients with WT JAK2 had the thrombosis history. The average age of patients with the JAK2V617F mutation exceeded the patients with wild type JAK2(P<0.05), whereas there is no statistical significance on sexual Athe counts of white cell and the occurance of complications (thrombosis) between the patients with and without the JAK2V617F mutation. All the patients have been followed up since onset and 22 patients have available results. Among them, 12 patients with the burden of JAK2V617F turned out to be MPDs, however only 1 out of 10 patients without this mutation also evolved to MPDs. Our results suggest that JAK2V617F mutation can occur in a certain percentage of these early stage of MPDs patients and has help to diagnose early MPDs. Because these patients might have a high rate of complications, proper treatment of the MPD including aspirin and/or cytoreductive therapy is recommended in latent MPDs patients associated with the JAK2V617F mutation.