Prognostically informative mutations of most frequent detection in patients with MPN
| Gene . | Polycythemia vera . | Essential thrombocythemia . | Primary myelofibrosis . | “Secondary” myelofibrosis . |
|---|---|---|---|---|
| JAK2 V617F | • Higher risk of thrombosis (included in revised IPSET) | • Intermediate prognosis and higher risk of thrombosis compared to patients with CALR mutation | ||
| CALR | • Lower risk of thrombosis compared to JAK2 mutated | • CALR type 1/like: improved survival compared to JAK2 V617F and “triple negative” • Improved outcome after SCT • Absence of CALR type 1/like included in MIPSS70/plus v2.0 • Absence of CALR mutation included in MYSEC-PM and MTSS scores | • Improved OS compared to JAK2 V617F and “triple negative” • Improved outcome after SCT • Absence of CALR mutation included in MYSEC-PM and MTSS scores | |
| MPL W515 | • Intermediate prognosis and higher risk of thrombosis compared to patients with CALR mutation | |||
| “Triple negative” | • Inferior OS and LFS compared to JAK2/CALR mutation (especially in pre-PMF) | |||
| JAK2 exon 12 | • Similar rates of thrombosis, evolution to post–PV-MF and BP, and survival to JAK2 V617F | |||
| ASXL1 | • “Adverse variant” associated with inferior OS and MFS • Included in MIPSS-PV | • “HMR variant” associated with inferior OS/LFS, lower PFS following SCT • Included in MIPSS70/plus v2.0 and GIPSS | ||
| EZH2 | • “Adverse variant” associated with inferior OS/LFS | • “HMR variant” associated with inferior OS • Included in MIPSS70/plus v2.0 | ||
| IDH1 IDH2 | • IDH1: “adverse variant” associated with inferior OS and LFS | • IDH2: “adverse variant” associated with inferior OS | • “HMR variants” associated with inferior OS/LFS and as lower PFS following SCT • Included in MIPSS70/plus v2.0 | • “Adverse variant” associated with lower PFS following SCT |
| SRSF2 | • “Adverse variant” associated with inferior OS • Included in MIPSS-PV | • “Adverse variant” associated with inferior OS/LFS • Included in MIPSS-ET | • “HMR variant” associated with inferior OS/LFS • Included in MIPSS70/plus v2.0 and GIPSS | |
| U2AF1 Q157 | • “HMR variant” associated inferior OS • Included in MIPSS70/plus v2.0 and GIPSS | |||
| U2AF1 or DNMT3A or CBL | • U2AF1: “adverse variant” associated with inferior OS/MFS • Included in MIPSS-ET | • “Adverse variant” associated with worse OS in SCT | • “Adverse variant” associated with worse OS in SCT | |
| RUNX1 | • “Adverse variant” associated with inferior OS and LFS | • “Adverse variant” associated with inferior OS/LFS | ||
| TP53 | • “Adverse variant” associated with inferior LFS | • “Adverse variant” associated with inferior OS/LFS • Included in MIPSS-ET | • “Adverse variant” associated with leukemic transformation | |
| LNK (SH2B3) | • “Adverse variant” associated with inferior OS | |||
| SF3B1 | • “Adverse variant” associated with inferior OS and MFS • Included in MIPSS-ET | |||
| RAS | • “Adverse variant” associated with inferior OS • Associated with JAKi-refractoriness |
| Gene . | Polycythemia vera . | Essential thrombocythemia . | Primary myelofibrosis . | “Secondary” myelofibrosis . |
|---|---|---|---|---|
| JAK2 V617F | • Higher risk of thrombosis (included in revised IPSET) | • Intermediate prognosis and higher risk of thrombosis compared to patients with CALR mutation | ||
| CALR | • Lower risk of thrombosis compared to JAK2 mutated | • CALR type 1/like: improved survival compared to JAK2 V617F and “triple negative” • Improved outcome after SCT • Absence of CALR type 1/like included in MIPSS70/plus v2.0 • Absence of CALR mutation included in MYSEC-PM and MTSS scores | • Improved OS compared to JAK2 V617F and “triple negative” • Improved outcome after SCT • Absence of CALR mutation included in MYSEC-PM and MTSS scores | |
| MPL W515 | • Intermediate prognosis and higher risk of thrombosis compared to patients with CALR mutation | |||
| “Triple negative” | • Inferior OS and LFS compared to JAK2/CALR mutation (especially in pre-PMF) | |||
| JAK2 exon 12 | • Similar rates of thrombosis, evolution to post–PV-MF and BP, and survival to JAK2 V617F | |||
| ASXL1 | • “Adverse variant” associated with inferior OS and MFS • Included in MIPSS-PV | • “HMR variant” associated with inferior OS/LFS, lower PFS following SCT • Included in MIPSS70/plus v2.0 and GIPSS | ||
| EZH2 | • “Adverse variant” associated with inferior OS/LFS | • “HMR variant” associated with inferior OS • Included in MIPSS70/plus v2.0 | ||
| IDH1 IDH2 | • IDH1: “adverse variant” associated with inferior OS and LFS | • IDH2: “adverse variant” associated with inferior OS | • “HMR variants” associated with inferior OS/LFS and as lower PFS following SCT • Included in MIPSS70/plus v2.0 | • “Adverse variant” associated with lower PFS following SCT |
| SRSF2 | • “Adverse variant” associated with inferior OS • Included in MIPSS-PV | • “Adverse variant” associated with inferior OS/LFS • Included in MIPSS-ET | • “HMR variant” associated with inferior OS/LFS • Included in MIPSS70/plus v2.0 and GIPSS | |
| U2AF1 Q157 | • “HMR variant” associated inferior OS • Included in MIPSS70/plus v2.0 and GIPSS | |||
| U2AF1 or DNMT3A or CBL | • U2AF1: “adverse variant” associated with inferior OS/MFS • Included in MIPSS-ET | • “Adverse variant” associated with worse OS in SCT | • “Adverse variant” associated with worse OS in SCT | |
| RUNX1 | • “Adverse variant” associated with inferior OS and LFS | • “Adverse variant” associated with inferior OS/LFS | ||
| TP53 | • “Adverse variant” associated with inferior LFS | • “Adverse variant” associated with inferior OS/LFS • Included in MIPSS-ET | • “Adverse variant” associated with leukemic transformation | |
| LNK (SH2B3) | • “Adverse variant” associated with inferior OS | |||
| SF3B1 | • “Adverse variant” associated with inferior OS and MFS • Included in MIPSS-ET | |||
| RAS | • “Adverse variant” associated with inferior OS • Associated with JAKi-refractoriness |
LFS, leukemia-free survival; MFS, myelofibrosis-free survival; PFS, progression-free survival.