Molecular diagnostics of myeloproliferative neoplasms

Abstract

Since the discovery of the JAK2 V617F mutation in the majority of the myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia and primary myelofibrosis ten years ago, further MPN-specific mutational events, notably in JAK2 exon 12, MPL exon 10 and CALR exon 9 have been identified. These discoveries have been rapidly incorporated into evolving molecular diagnostic algorithms. Whilst many of these mutations appear to have prognostic implications, establishing MPN diagnosis is of immediate clinical importance with selection, implementation and the continual evaluation of the appropriate laboratory methodology to achieve this diagnosis similarly vital. The advantages and limitations of these approaches in identifying and quantitating the common MPN-associated mutations are considered herein with particular regard to their clinical utility. The evolution of molecular diagnostic applications and platforms has occurred in parallel with the discovery of MPN-associated mutations, and it therefore appears likely that emerging technologies such as next-generation sequencing and digital PCR will in the future play an increasing role in the molecular diagnosis of MPN.

Mutation status of essential thrombocythemia and primary myelofibrosis defines clinical outcome

“…TET2, DNMT3A and ASXL1. 10 In the current study, mutations were found in 35 additional genes (Figure 3 and Online Supplementary Table S3). All but one patient with MPL mutated ET had additional mutations, while in 39% of ET cases with JAK2 mutation (n=7) and 28% with CALR mutation (n=5) no additional mutations were found.…”

<b><i>JAK2</i></b>^V617F, <b><i>CALR</i></b>, and <b><i>MPL</i></b> Mutations and Bone Marrow Histology in Patients with Essential Thrombocythaemia

“…Indeed, apart from JAK2 V617F , MPL , and CALR mutations, several other gene mutations have been described: TET2 (in 5% of cases), DNMT3A (in 1–5%), and ASXL1 (in 2–5%) [16]. Thirty-five other gene mutations have been reported [7].…”

Philadelphia-negatív krónikus Myeloproliferativ Neoplasia Magyarországi Regiszter. Polycythaemia verás betegeink adatainak elemzése

“…A Philadelphia-negatív klasszikus myeloproliferativ neoplasiák (MPN) köré-be tartozik az essentialis thrombocythaemiával (ET) és a primer myelofibrosissal (PMF) együtt. A kórkép kialakulására jellemző a JAK-STAT jelátviteli útvonal folyamatos, konstitucionális aktivációja, amely a myeloproliferatióhoz vezet [1,2].…”