The JAK2V617F mutation is detectable at very low level in peripheral blood of healthy donors

The JAK2 V617F mutation is detectable in granulocyte populations at greater than two copies per cell among individuals with myeloproliferative disorders

“…The JAK2V617F mutation is detectable in granulocyte populations at greater than 2 copies per cell among individuals with myeloproliferative disorders Unlike previous publications (for a review see McClure et al 1 ), we recently reported the detection of the JAK2V617F mutation at very low levels in peripheral blood of healthy individuals. 2 Using a sensitive polymerase chain reaction (PCR) method specific to the JAK2V617F mutation, Hammond et al 3 reported also very low copies of this mutation in granulocyte populations of normal individuals that they assumed to represent nonspecific amplification of the wild-type JAK2 allele.…”

JAK2 mutation and disease phenotype: a double L611V/V617F in cis mutation of JAK2 is associated with isolated erythrocytosis and increased activation of AKT and ERK1/2 rather than STAT5

“…PU.1 is necessary for the generation and function of macrophages and granulocytes through the regulation of essential myeloid genes such as the granulocyte/macrophage colony-stimulating factor receptor (GM-CSFR), the macrophage CSF (M-CSF), the granulocyte CSF (G-CSF), CD11b, myeloperoxidase, lysozyme, neutrophil elastase, CD45, and others. [1][2][3] Anti-apoptotic Bcl2 proteins are frequently overexpressed during tumorigenesis 4 and three of them are expressed in myeloid cells: BCL2A1 (also designated as A1 or BFL-1) and Mcl-1 in neutrophils, whereas BCL2A1 and Bcl-x L can both be upregulated in macrophages by proinflammatory stimuli in vitro. Sevilla et al 5 reported that PU.1 together with another Ets-family member, Ets2, transactivate the Bcl-x L promoter and increase macrophage survival.…”

“…Indeed healthy donors were reported positive for JAK2-V617F using nested PCR assays, and the repeated occurrence of the V617F mutation of JAK2 has been demonstrated in essential thrombocythemia (ET) and in PV. [3][4][5] In addition, in 2 PV patients, JAK2-V617F and mutations in exon 12 of JAK2 co-existed in separate sub-clones originating from a single progenitor in one case, or from unrelated hematopoietic stem cells in the other case. 6,7 V617F-positive PV patients with additional mutation(s) in exon 14 of JAK2 (V615L, C616Y, C618R and D620E) are also evidence of multiple JAK2 mutations.…”

Myeloproliferative Neoplasm or Reactive Process? A Rare Case of Acute Myeloid Leukemia and Transient Post-Treatment Megakaryocytic Hyperplasia with JAK-2 Mutation

“…High frequency of JAK2 mutation in MPN makes JAK2 mutation testing a frontline screen for highly suspected MPN. Quantitative JAK2 mutation testing can not only provide prognostic information about MPN and monitor minimal residual disease after stem cell transplant for JAK2-positive patients with myelofibrosis but also be used to monitor disease progression and response to therapy [10][11][12]. The JAK2 inhibitor ruxolitinib was approved for the treatment of MF and more recently for the treatment of PV with inadequate response or intolerant adverse effects to hydroxyurea.…”