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Editorial
. 2010 Apr;95(4):526-9.
doi: 10.3324/haematol.2009.019570.

Molecular basis and clonal evolution of myeloproliferative neoplasms

Roland Jäger, Robert Kralovics
Editorial

Molecular basis and clonal evolution of myeloproliferative neoplasms

Roland Jäger et al. Haematologica. 2010 Apr.
No abstract available

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Figures

Figure 1.
Figure 1.
Mechanisms and pathways targeted by mutations in MPN. Schematic diagram of pathways involved in MPN pathogenesis. Red boxes summarize germ line and somatic mutations in MPN and MPN-like phenotypes. Clonal advantage based on cytokine hypersensitivity can be triggered by genetic defects directly targeting cytokine receptors, such as MPL mutations and EPO-R C-terminal truncations, as well as mutations affecting elements of downstream signaling cascades. Defects identified so far in MPN predominantly activate the JAK-STAT and the mitogen-activated protein kinase (MAPK) pathways. Gain-of-function mutations in JAK2 (JAK2-V617F and JAK2 exon 12 mutations) directly affect signal transduction, whereas loss of function mutations in CBL and NF1 intervene indirectly. The ubiquitin ligase CBL regulates the degradation of surface receptors and JAK2. NF1, a GTPase activating protein decreases signal potential of Ras, an important protooncogene in the MAPK pathway. Besides defects in cytokine signal transduction, mutations potentially directly affecting gene transcription have been found in TET2. TET2 might be involved in epigenetic transcriptional regulation by enzymatically catalyzing the conversion of 5-methylcytosine to 5-hydroxymethylcytosine, as shown for another TET family member TET1.
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