Genes involved in the pathogenesis of MPN
| Gene . | Localization . | Function . | Comment . | Disease (frequency) . | References . |
|---|---|---|---|---|---|
| JAK2 | 9p24 | Tyrosine kinase, signaling | Gain of function | PV (95%-99%), ET (50%-70%), PMF (40%-50%) | 6,,–9,11,12 |
| MPL | 1p34 | Receptor, signaling | Gain of function | ET (4%), PMF (11%) | 13,,–16 |
| LNK | 12q24 | Adaptor, signal regulation | Loss of function | ET (< 5%), PMF (< 5%), JAK2 mutation-negative erythrocytosis (25%), post-MPN AML (13%) | 17,–19 |
| CBL | 11q23 | Adaptor, E3 ubiquitin ligase, signal regulation | Dominant negative | PMF (6%), post-MPN AML | 20,21 |
| SOCS1 | 16p13.2 | E3 ubiquitin ligase, signal regulation | Methylation | ET (14%-25%), PV (11%-13%), PMF (17%) | 22,23 |
| SOCS2 | 12q22 | E3 ubiquitin ligase, signal regulation | Methylation | All MPN (28%) | 24 |
| SOCS3 | 17q25.3 | E3 ubiquitin ligase, signal regulation | Methylation, mutation | ET (10%), PV (22%) | 22,25,–27 |
| NRAS | 1p13.2 | GTPase, signaling | Gain of function | post-MPN AML (7%-13%) | 21 |
| NF1 | 17q11.2 | RAS signaling regulation | Deletion | PMF (0%-6%), post ET/PV MF (14%) | 28,29 |
| TET2 | 4q24 | DNA hydroxymethylation | Loss of function | PV (15%), ET (4%-11%), PMF (19%), post-MPN AML (26%) | 30,,–33 |
| ASXL1 | 20q11.21 | Chromatin modifications | Loss of function | PV and ET (< 7%) PMF (19%-40%), post-MPN AML (19%) | 34,35 |
| EZH2 | 7q35 | Chromatin methylation | Loss of function | PV (3%), PMF (13%) | 36,–38 |
| IKZF1 | 7p12 | Transcription factor, lymphopoiesis | Deletion | post-MPN AML (21%) | 39 |
| RUNX1 | 21q22.3 | Transcription factor, hematopoiesis | Loss of function | post-MPN AML (37%) | 21,40 |
| RB | 13q14 | Cell cycle, apoptosis | Deletion | PMF (19%) | 29 |
| TP53 | 17p13.1 | Cell cycle, apoptosis | Loss of function | post-MPN AML (20%) | 21,41 |
| IDH1 | 2q33.3 | Metabolism | Neomorphic enzyme | PMF (2%), post-MPN AML (8%) | 42 |
| IDH2 | 15q26.1 | Metabolism | Neomorphic enzyme | PMF (2%), post-MPN AML (18%) | 42 |
| Gene . | Localization . | Function . | Comment . | Disease (frequency) . | References . |
|---|---|---|---|---|---|
| JAK2 | 9p24 | Tyrosine kinase, signaling | Gain of function | PV (95%-99%), ET (50%-70%), PMF (40%-50%) | 6,,–9,11,12 |
| MPL | 1p34 | Receptor, signaling | Gain of function | ET (4%), PMF (11%) | 13,,–16 |
| LNK | 12q24 | Adaptor, signal regulation | Loss of function | ET (< 5%), PMF (< 5%), JAK2 mutation-negative erythrocytosis (25%), post-MPN AML (13%) | 17,–19 |
| CBL | 11q23 | Adaptor, E3 ubiquitin ligase, signal regulation | Dominant negative | PMF (6%), post-MPN AML | 20,21 |
| SOCS1 | 16p13.2 | E3 ubiquitin ligase, signal regulation | Methylation | ET (14%-25%), PV (11%-13%), PMF (17%) | 22,23 |
| SOCS2 | 12q22 | E3 ubiquitin ligase, signal regulation | Methylation | All MPN (28%) | 24 |
| SOCS3 | 17q25.3 | E3 ubiquitin ligase, signal regulation | Methylation, mutation | ET (10%), PV (22%) | 22,25,–27 |
| NRAS | 1p13.2 | GTPase, signaling | Gain of function | post-MPN AML (7%-13%) | 21 |
| NF1 | 17q11.2 | RAS signaling regulation | Deletion | PMF (0%-6%), post ET/PV MF (14%) | 28,29 |
| TET2 | 4q24 | DNA hydroxymethylation | Loss of function | PV (15%), ET (4%-11%), PMF (19%), post-MPN AML (26%) | 30,,–33 |
| ASXL1 | 20q11.21 | Chromatin modifications | Loss of function | PV and ET (< 7%) PMF (19%-40%), post-MPN AML (19%) | 34,35 |
| EZH2 | 7q35 | Chromatin methylation | Loss of function | PV (3%), PMF (13%) | 36,–38 |
| IKZF1 | 7p12 | Transcription factor, lymphopoiesis | Deletion | post-MPN AML (21%) | 39 |
| RUNX1 | 21q22.3 | Transcription factor, hematopoiesis | Loss of function | post-MPN AML (37%) | 21,40 |
| RB | 13q14 | Cell cycle, apoptosis | Deletion | PMF (19%) | 29 |
| TP53 | 17p13.1 | Cell cycle, apoptosis | Loss of function | post-MPN AML (20%) | 21,41 |
| IDH1 | 2q33.3 | Metabolism | Neomorphic enzyme | PMF (2%), post-MPN AML (8%) | 42 |
| IDH2 | 15q26.1 | Metabolism | Neomorphic enzyme | PMF (2%), post-MPN AML (18%) | 42 |
AML indicates acute myeloid leukemia; ET, essential thrombocythemia; JAK2, Janus kinase 2; MPN, myeloproliferative neoplasms; PMF, primary myelofibrosis; and PV, polycythemia vera.