Somatic mutations described in classic myeloproliferative neoplasms including primary myelofibrosis, polycythemia vera and essential thrombocythemia
| Mutations . | Chromosome location . | Mutational frequency, % . | Pathogenetic relevance . |
|---|---|---|---|
| JAK2 (Janus kinase 2) | 9p24 | PV ∼ 9613 | Contributes to abnormal myeloproliferation and progenitor cell growth factor hypersensitivity13 |
| JAK2V617F exon 14 mutation13 | ET ∼ 5513 | ||
| PMF ∼ 6513 | |||
| BP-MPN ∼ 5013 | |||
| JAK2 exon 12 mutation13 | 9p24 | PV ∼ 313 | Contributes to primarily erythroid myeloproliferation13 |
| MPL (myeloproliferative leukemia virus oncogene) MPN-associated mutations involve exon 1013 | 1p34 | ET ∼ 313 | Contributes to primarily megakaryocytic myeloproliferation13 |
| PMF ∼ 1013 | |||
| BP-MPN ∼ 513 | |||
| TET2 (TET oncogene family member 2) MPN-associated mutations occur across several of the gene's 12 exons13 | 4q24 | PV ∼ 1613 | May contribute to epigenetic dysregulation (TET proteins catalyze conversion of 5-methylcytosine to 5-hydroxymethylcytosine) 24 |
| ET ∼ 513 | |||
| PMF ∼ 1713 | |||
| BP-MPN ∼ 1713 | |||
| ASXL1 (additional sex combs-like 1) exon 12 mutations | 20q11.1 | CP-MPN ∼ rare87 | Wild-type ASXL1 is needed for normal hematopoiesis88 and might be involved in transcriptional repression23 |
| PMF ∼ 1389 | |||
| BP-MPN ∼ 1889 | |||
| CBL (Casitas B-lineage lymphoma protooncogene) exon 8/9 mutations90 | 11q23.3 | PV ∼ rare90 | CBL is an E3 ubiquitin ligase that marks mutant kinases for degradation and transforming activity requires loss of wild-type CBL91 |
| ET ∼ rare90 | |||
| MF ∼ 690 | |||
| IDH1/IDH2 (isocitrate dehydrogenase) exon 4 mutations45 | 2q33.3/ | PV ∼ 245 | Induces formation of 2-hydroxyglutarate, a possible oncoprotein25 |
| 15q26.1 | ET ∼ 145 | ||
| PMF ∼ 445 | |||
| BP-MPN ∼ 2045 | |||
| IKZF1 (IKAROS family zinc finger 1) (mostly deletions including intragenic92 ) | 7p12 | CP-MPN ∼ rare92 | Transcription regulator and putative tumor suppressor93 |
| BP-MPN ∼ 1992 | |||
| LNK (as in Links) also known as SH2B3 (a membrane-bound adaptor protein) MPN-associated mutations were monoallelic and involved exon 218,94 | 12q24.12 | PV ∼ rare94,95 | Wild-type LNK is a negative regulator of JAK2 signaling96 |
| ET ∼ rare18,94 | |||
| PMF ∼ rare18,94 | |||
| BP-MPN ∼ 1094 | |||
| EZH2 (enhancer of zeste homolog 2) both monoallelic and biallelic mutations occur in MPN, involving exons 10, 18, and 20, and are thought to be inactivating14 | 7q36.1 | PV ∼ 314 | Wild-type EZH2 is part of a histone methyltransferase and might function both as a tumor suppressor (myeloid malignancies) 14 and an oncogene (other tumors) |
| PMF ∼ 788 | |||
| MF ∼ 1314 |
| Mutations . | Chromosome location . | Mutational frequency, % . | Pathogenetic relevance . |
|---|---|---|---|
| JAK2 (Janus kinase 2) | 9p24 | PV ∼ 9613 | Contributes to abnormal myeloproliferation and progenitor cell growth factor hypersensitivity13 |
| JAK2V617F exon 14 mutation13 | ET ∼ 5513 | ||
| PMF ∼ 6513 | |||
| BP-MPN ∼ 5013 | |||
| JAK2 exon 12 mutation13 | 9p24 | PV ∼ 313 | Contributes to primarily erythroid myeloproliferation13 |
| MPL (myeloproliferative leukemia virus oncogene) MPN-associated mutations involve exon 1013 | 1p34 | ET ∼ 313 | Contributes to primarily megakaryocytic myeloproliferation13 |
| PMF ∼ 1013 | |||
| BP-MPN ∼ 513 | |||
| TET2 (TET oncogene family member 2) MPN-associated mutations occur across several of the gene's 12 exons13 | 4q24 | PV ∼ 1613 | May contribute to epigenetic dysregulation (TET proteins catalyze conversion of 5-methylcytosine to 5-hydroxymethylcytosine) 24 |
| ET ∼ 513 | |||
| PMF ∼ 1713 | |||
| BP-MPN ∼ 1713 | |||
| ASXL1 (additional sex combs-like 1) exon 12 mutations | 20q11.1 | CP-MPN ∼ rare87 | Wild-type ASXL1 is needed for normal hematopoiesis88 and might be involved in transcriptional repression23 |
| PMF ∼ 1389 | |||
| BP-MPN ∼ 1889 | |||
| CBL (Casitas B-lineage lymphoma protooncogene) exon 8/9 mutations90 | 11q23.3 | PV ∼ rare90 | CBL is an E3 ubiquitin ligase that marks mutant kinases for degradation and transforming activity requires loss of wild-type CBL91 |
| ET ∼ rare90 | |||
| MF ∼ 690 | |||
| IDH1/IDH2 (isocitrate dehydrogenase) exon 4 mutations45 | 2q33.3/ | PV ∼ 245 | Induces formation of 2-hydroxyglutarate, a possible oncoprotein25 |
| 15q26.1 | ET ∼ 145 | ||
| PMF ∼ 445 | |||
| BP-MPN ∼ 2045 | |||
| IKZF1 (IKAROS family zinc finger 1) (mostly deletions including intragenic92 ) | 7p12 | CP-MPN ∼ rare92 | Transcription regulator and putative tumor suppressor93 |
| BP-MPN ∼ 1992 | |||
| LNK (as in Links) also known as SH2B3 (a membrane-bound adaptor protein) MPN-associated mutations were monoallelic and involved exon 218,94 | 12q24.12 | PV ∼ rare94,95 | Wild-type LNK is a negative regulator of JAK2 signaling96 |
| ET ∼ rare18,94 | |||
| PMF ∼ rare18,94 | |||
| BP-MPN ∼ 1094 | |||
| EZH2 (enhancer of zeste homolog 2) both monoallelic and biallelic mutations occur in MPN, involving exons 10, 18, and 20, and are thought to be inactivating14 | 7q36.1 | PV ∼ 314 | Wild-type EZH2 is part of a histone methyltransferase and might function both as a tumor suppressor (myeloid malignancies) 14 and an oncogene (other tumors) |
| PMF ∼ 788 | |||
| MF ∼ 1314 |
MPN indicates myeloproliferative neoplasms; ET, essential thrombocythemia; PV, polycythemia vera; PMF, primary myelofibrosis; MF includes both PMF and post-ET/PV myelofibrosis; BP-MPN, blast phase MPN; and CP-MPN, chronic phase MPN.