Guide to  

                          the Genetics of

                  Polycythaemia Vera (Rubra)


                  Essential Thrombocythaemia

                              'PV & ET'

The JAK2 V617F mutation

In 2005 several research groups announced that a genetic mutation had been found to be present in nearly all people wtih PV, and about half of the people with ET. This mutation JAK2 V617F is not present in the normal cells of the body, but only in the 'clone' of cells that is found in PV, ET and some other conditions. Until now JAK2 V617F has been classed as a cancer-driver mutation; but in PV & ET it does not appear to be linked to cancer - and other changes are needed before a cancer develops. The mutation itself is a change of a 'G' (for guanine) to 'T' (for thiamine) in the 617 th. amino acid in the JAK2 gene on chromosome 9. This mutation can also be described using the SNP ID rs77375493. The JAK2 V617F would appear to be maternally inherited as it would appear to be implausible that this unusual mutation can arise by chance in so many people. Therefore it follows that a number of families have clonal cells with the JAK2 V617F mutation; whereas in other families the mutation is absent. A working figure for the incidence of families that carry JAK2 V617F might be that 1 family in 500. But this has yet to be proved. Present blood test can detect cells with the JAK2 V617F mutation when the proportion of clonal cels is perhaps at a 0.1% level (put simply when 1 in 1,000 bone marrow cells belong to the clone); but it would appear very likely that many people would be found to be JAK2 V617F positive if the test were much more sensitive. Just being positive for the JAK2 V617F mutation, but without symptoms, may predispose the person to an increased risk of venous or arterial thrombosis; and prophylaxis with daily aspirin may be appropriate.