I know this probably isn't a lot of help, but I always google things like this or look online in a medical dictionary. I did some research for you, I don't know if you can understand any of this but here is part of the research article:
A Unique Acquired Clonal JAK2 Mutation Is Found in PV, ET and IMF
A recurrent unique acquired clonal mutation in JAK2 was recently found by five different research teams. This mutation was observed in a majority of PV patients and a significant proportion of patients with other MPDs, including ET, IMF and some rare MPDs. Our group worked on the mechanisms leading to EEC formation and identified JAK2 as a potential candidate gene because JAK2 kinase inhibitors as well as a JAK2 siRNA inhibited EEC.26 Three other teams sequenced JAK2 as a consequence of kinase gene sequencing in MPDs.27–29 Finally, one team mapped the minimal region on chromosome 9p to a 6.2 Mbp interval that contains several genes including JAK2.30
A unique valine to phenylalanine substitution at position 617 (V617F) in the pseudokinase JAK2 domain has been identified. The incidence of this mutation in PV patients is very high (78% of 506 patients), ranging from 65% to 97% depending on the study. These variations in percentage of patients involved is likely due to the clinical criteria used for diagnosis, either the Polycythemia Study Group (PSVG) or World Health Organization (WHO) classifications, and also the sensitivity of the assay used to detect JAK2 V617F. The JAK2 V617F mutation was, however, not found in some patients who were shown to have both monoclonal hematopoiesis and to form EEC, demonstrating that some cases of true PV are related to other molecular defects (our own unpublished results). Sequencing of genomic DNA from granulocytes was used in most studies to detect the mutation.26–30 The sensitivity of this technique is difficult to assess precisely, but it is likely that a threshold of 5% to 15% cells harboring the mutation is required for such an analysis to be positive. In one study, the mutation was detected in 97% of the PV samples (71/73) with a sensitive PCR assay.27 The variable prevalence estimates of the JAK2 V617F in MPD patients therefore may be related to the fact that in some patients with JAK2 V617F, less than 10% of granulocyte JAK2 alleles are JAK2 V617F alleles, suggesting that MPD patients could retain normal stem cell clones. These data are surprising since PV is considered to be a clonal disease with the majority of myeloid cells, including granulocytes, belonging to the clone. Further studies are, therefore, required to confirm these data.
The JAK2 mutation is somatic and occurs at the level of a hematopoietic stem cell. In all studies, the mutated JAK2 was found in myeloid cells, i.e., bone marrow cells, granulocytes, platelets and erythroblasts derived from CD34+ cells, but not in T cells. In addition, mutant JAK2 was found in hematopoietic colonies derived from hematopoietic progenitor cells.27 In contrast, the mutation was not present in non-hematopoietic cells in most patients.28,30 Since familial MPDs have been reported, it was important to know if this mutation can be germ-line. Linkage analysis did not show co-segregation with the 9p locus suggesting that the V617F substitution occurred as a somatic mutation even in these families. The similar frequency of the V617F mutation in familial and sporadic PV is in favor of this assumption31 (Najman, personal communication). In one study, however, the mutation was detected in buccal swabs of 4% of the patients.28 This finding may be due to contamination by granulocytes because in another study two patients positive for the mutation after analysis of buccal swabs were negative in cells within hair follicles.30
The JAK2 V617F mutation has been found in other Bcr-Abl negative MPDs with a frequency of about 50% in IMF and more variably in ET (from 25% to 57%).26–28,30 In many cases, the mutation was detected only at the threshold of the sequencing technique in ET. This may signify that hematopoiesis is not entirely clonal in many ET patients and that the mutation must be searched by more sensitive techniques or directly in platelets. The JAK2 mutation was recently found in other MPDs with a frequency of about 20% in atypical CML and unclassified MDS and at a lower frequency (2%–3%) in HES, CMML or SM.32 By contrast, the mutation was not detected in AML, except for AML secondary to an MPD or megakaryocytic leukemia.32,33 Thus, the presence of JAK2 V617F mutation provides a means of developing a new classification of MPDs that includes the majority of PV cases, a large fraction of cases of IMF and some cases of ET (the precise frequency remains to be determined) and some atypical MPDs. This mutation opens new avenues both for the diagnosis and the classification of MPDs.
