Laboratory Diagnostics of Myeloproliferative Neoplasms

Susanne Schnittger1,*

1MLL Munich Leukemia Laboratory, Munich, Germany

The first mutation detected in BCR-ABL1 negative myeloproliferative neoplasms (MPN) was JAK2V617F and has revolutionized diagnostics of MPN almost 10 years ago. In 2008 not only JAK2V617F, but also JAK2exon12 and MPLW515 were implemented into the WHO classification to foster diagnosis of the classical three MPN polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF). In addition, KITD816V was included as a criterion for mastocytosis and PDGFR rearrangements even were selected to define a new entity. Since then new technologies mainly based on next generation sequencing strategies have accelerated the detection of new gene mutations in MPN. For example, CALR mutations are now nearly completely filling the gap of JAK2V617F negative ET and PMF. SETBP1 mutations have been found to be characteristic for atypical CML (aCML) and accelerated stage MPN. CSF3R mutations are not only helpful to diagnose chronic neutrophilic leukemia (CNL) but, in addition, are promising indicators for therapies with JAK or SRC kinase inhibitors. CMML and other more accelerated MPN are characterized by sets of various gene mutations e.g. in ASXL1, CBL, EZH2, NRAS, KRAS, RUNX1, SRSF2 and TET2. It has become clear that some of these mutations like JAK2exon12, MPLW515, KITD816 and PDGFR rearrangements are useful to further subclassify MPN. Other gene mutations including JAK2V617F, TET2, EZH2 are helpful to discriminate MPN from reactive disorders. Based on these options mutation analyses have rapidly found their way to routine diagnostics. We analysed a total of 30,000 cases with MPN and applied patient specific combinations of these markers. A focus will be how to select the right markers and methods that provide all important information to finally find the right diagnosis in the context of other diagnostic tools. This data will show that mutation analysis improved the diagnostic work up for MPN in the last 10 years leading to entity specific diagnosis and also to targeted therapies

Keywords: Biomarker, Cancer, Genomics