“The JAK2 V617F mutation is detectable in granulocyte populations at greater than two copies per cell among individuals with myeloproliferative disorders”, by El Housni et al.

Abstract

method used is known to potentially generate artefact of the PCR. In our situation, we still believe that normal peripheral blood cells harbouring a JAK2V617F mutation do really exist, as the detection of a mutated allele was obtained with great reproducibility in several genomic DNA and cDNA preparations for each of our healthy positive controls. Furthermore, a mutated sequence was recurrently observed in two of these individuals. Our ability to get a mutated sequence despite a very low level of JAK2V617F-mutated alleles was due to the use of locked nucleic acid (LNA) oligonucleotide that limited the amplification of the wild-type JAK2 sequence and allowed thus to enrich sufficiently the PCR tube with mutated amplicons.Beside the debate regarding the presence or not of JAK2V617F mutated allele in normal population, Hammond et al. provide interesting results in that they were able to detect gains of the mutated allele in some of their cases of myeloproliferative disorders. These findings are reminiscent of previously described situations where oncogenes (such as mutant EGFR (epidermal growth factor receptor), Met or RET) require either duplication/ amplification of the mutant allele or loss of the wild-type allele to attain optimal tumorigenic potential. [4][5][6] If confirmed by other studies, the data proposed by Hammond et al. will bring further insights into the possible molecular mechanisms by which the JAK2V617F mutation contributes to the development of the disease.