Targeted Re-sequencing for Diagnosis and Prognosis in MPNs

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High throughput Next Generation Sequencing (NGS) is becoming increasing important in the routine diagnosis and molecular monitoring of cancer. The myeloproliferative neoplasms (MPNs) are a heterogeneous group of blood disorders characterised by unrestrained proliferation of mature blood cell types. Unlike the scenario in chronic myeloid leukemia, there a different driver mutations which result in MPNs. Gain of function mutations in JAK2 (V617F), CALR, and MPL (the thrombopoietin receptor) are the most common driver mutations but about 15% of MPNs do no harbour mutations in any of these genes. They are commonly referred to as ‘triple negative’ MPNs. The precise diagnosis in some of these cases is difficult; they often do not fit easily into one of the WHO subtypes. We and other groups have developed extensive gene panels to detect the vast majority of rarer mutations which drive MPNs as well as detect secondary mutations in genes with prognostic significance (1,2). Panels of this type will be a very cost-effective method for accurate molecular diagnosis and for clinical decision making based on prognosis. Future clinical trials will test whether early intervention in patients with high risk genetic signatures is beneficial.


  1. Rapid molecular profiling of myeloproliferative neoplasms using targeted exon re-sequencing of 86 genes involved in JAK-STAT signalling and epigenetic regulation. Graham W. Magor, Michael R. Tallack, Nathan M. Klose, Debbie Taylor, Darren Korbie, Peter Mollee, Matt Trau and Andrew C. Perkins. Journal of Molecular Diagnostics (2016) Sep; 18(5):707-18.
  2. Mutations and prognosis in primary myelofibrosis. Vannucchi AM, Lasho TL, Guglielmelli P, Biamonte F, Pardanani A, Pereira A, Finke C, Score J, Gangat N, Mannarelli C, Ketterling RP, Rotunno G, Knudson RA, Susini MC, Laborde RR, Spolverini A, Pancrazzi A, Pieri L, Manfredini R, Tagliafico E, Zini R, Jones A, Zoi K, Reiter A, Duncombe A, Pietra D, Rumi E, Cervantes F, Barosi G, Cazzola M, Cross NC, Tefferi A. Leukemia (2013) Sep;27(9):1861-9.