Table 2.
Non-driver genes implicated in BCR-ABL1 negative Myeloproliferative Neoplasms *.
| Gene | Function | Prognostic Implication |
|---|---|---|
| ASXL1 | Histone modification (Chromatin binding protein) | Also identified in age-related clonal hematopoiesis, CML and MPNs—associated with unfavorable prognosis and rapid progression to AML |
| 20q11 | ||
| EZH2 | Histone modification (loss of function of H3K27 methyltransferase) | Implicated in Post-ET and Post-PV MF, unfavorable prognosis in PMF |
| 7q35-36 | ||
| DNMT3A | DNA methylation (DNA methylase) | Somatic mutations identified in age-related clonal hematopoiesis, CML and MPNs—associated with rapid disease progression |
| 2p23 | ||
| IDH1/2 | DNA methylation (converts isocitrate to α-ketoglutarate) | Implicated in disease progression |
| 2q33.3/15q26.1 | ||
| TET2 | DNA methylation (essential in myelopoiesis) | Somatic mutations identified in age-related clonal hematopoiesis, CML and MPNs—associated with rapid disease progression |
| 4q24 | ||
| SRSF2 | RNA splicing/spliceosome assembly | Associated with progression to Myelofibrosis, downregulates EZH2, unfavorable prognosis in PMF |
| 12q25.1 | ||
| SF3B1 | RNA splicing/spliceosome assembly | Associated with the presence of ringed sideroblasts, increased incidence of anemia |
| 2q33.1 | ||
| U2AF1 | RNA splicing/spliceosome assembly | Associated with disease progression to AML, unfavorable prognosis in PMF |
| 21q22.3 | ||
| LNK | Negative regulator of JAK2 | Implicated in disease progression, also found in familial cases of erythrocytosis |
| 12q24 | ||
| TP53 | Transcription factor (involved in cell cycle regulation, DNA repair and apoptosis) | TP53 associated with poor prognosis, also associated with disease progression to AML (in <3% cases) |
| 17p13.1 | ||
| ETV6 | Transcription factor | Also associated with disease progression to AML (in <3% cases) |
| 12p13 | ||
| RUNX1 | Transcription factor (hematopoiesis) | Also associated with disease progression to AML (in <3% cases), also seen in secondary AML (about 30% cases) |
| 21q22.3 | ||
| CBL | Cytokine receptor in signal transduction pathways | Implicated in AML progression (rare in PMF, but found in 10–15% secondary AML) |
| 11q23.3 | ||
| FLT3 | Cytokine receptor in signal transduction pathways | Implicated in AML progression (rare in PMF, but found in 10–15% secondary AML) |
| 13q12 | ||
| NRAS | MAPK signaling pathway | Implicated in AML progression (rare in PMF, but found in 10–15% secondary AML) |
| 1p13.2 | ||
| NF1 | MAPK signaling pathway | Implicated in AML progression (rare in PMF, but found in 10–15% secondary AML) |
| 17q11 |