Table 2.
Somatic mutations and their frequencies in PMF
| Mutations | Frequency in PMF, % | Pathologic relevance |
|---|---|---|
| JAK2-V617F exon 14 | 65 | Contributes to abnormal myeloproliferation and progenitor cell growth factor hypersensitivity |
| CALR exon 9 deletions and insertions | 25 | Wild-type CALR is a multifunctional Ca2+-binding protein chaperone mostly localized in the endoplasmic reticulum |
| MPL exon 10 | 10 | Contributes to megakaryocytic proliferation |
| LNK (membrane bound adapter protein) exon 2 | Rare | Wild-type LNK is a negative regulator of JAK2 signaling |
| TET2 involving several exons | 17 | TET proteins catalyze conversion of 5-methylcytosine to 5-hydroxymethylcytosine, which begin the demethylation process of DNA. Mutant TET2 did not seem to affect survival, leukemic transformation, thrombosis risk, or cytogenetic profile in either PV or PMF |
| ASXL1 exon 12 | 13 | Wild-type ASXL1 is needed for normal hematopoiesis and might be involved in coactivation of transcription factors and transcriptional repression |
| IDH1/IDH2 exon 4 | 4 | Mutant IDH enzymes convert α-ketoglutarate to the oncometabolite 2-hydroxyglutarate, which results in aberrant hypermethylation of DNA |
| EZH2 (enhancer of zeste homolog 2), several exons | 7 | Wild-type EZH2 is part of a histone methyltransferase associated with H3Lys27 trimethylation. MPN-associated EZH2 mutations might have a tumor suppressor activity, which contrasts with the gain-of-function activity for lymphoma-associated EZH2 mutations |
| DNMT3A | 7 | DNA methyltransferases are essential in establishing and maintaining DNA methylation patterns in mammals |
| CBL (Casitas B lineage lymphoma protooncogene) exons 8, 9 | 6 | CBL is an E3 ubiquitin ligase that marks mutant kinases for degradation, transforming activity requires loss of this function |
| TP53 exons 4–9 | 4 | A tumor suppressor protein that targets genes that regulate cell cycle arrest, apoptosis and DNA repair |
| SF3B1 (splicing factor 3B subunit 1) exon 14–15 | 7 | SF3B1 is a component of the RNA spliceosome. SF3B1 mutations are closely associated with ring sideroblasts |
| SRSF2 exon2 | 17 | SRSF2 is a component of the RNA spliceosome, whose dysfunction promotes defects in alternative splicing. It is associated with anemia and thrombocytopenia |
| U2AF1 | 16 | U2AF1 is a subunit of the U2 small nuclear ribonucleoprotein auxiliary factor involved in pre-mRNA processing, associated with anemia and thrombocytopenia |