Features of 16 patients with progression to acute leukemia after a JAK2-mutant MPN
| Pt . | Myeloproliferative neoplasm . | At transformation to AML . | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age at diagnosis, y/sex . | MPN . | JAK2 mutation status . | Therapy . | Disease duration, y . | Sample from MPN phase . | JAK2 mutation status . | Cytogenetic analysis . | Additional mutations . | Altered gene expression . | ||
| 1 | 63/M | PMF | JAK2 V617F | HC, AN | 2 | BM at diagnosis | Het | 3 copies AML1* | NRAS G12S, RUNX1 D171N | — | |
| 2 | 47/M | ET->MF | JAK2 V617F | HC | 16 | Grans 1 y pre-AML | Hom | inv(3), del(7) | NRAS G12D | ↑WT1, ↑EVI1 | |
| 3 | 47/F | PV->MF | JAK2 V617F | HC, IFN | 10 | Grans 1 y pre-AML | Hom | ND | RUNX1 N119K | ↑WT1 | |
| 4 | 58/M | PMF | JAK2 V617F | none | 1 | None | Hom | ND | RUNX1 G138V | ↑WT1 | |
| 5 | 70/M | Probable PMF | JAK2 V617F | none | NA | NA | Hom | add(8), del(7q) | RUNX1 D171N | ↑WT1 | |
| 6 | 72/M | PMF | JAK2 V617F | HC | 8 | None | Hom | ND | — | ↑WT1, ↑JAK2 | |
| 7 | 67/M | ET->MF | JAK2 V617F | HC | 6 | Grans 1.5 y pre-AML | Hom | der5, t(5;17) | TP53 R248Q | ↑WT1 | |
| 8 | 43/M | PV | JAK2 N542-E543del | BU, P32, HC | 26 | None | Wild-type | del(20q) | TET2 D1242V, RUNX1 H215X | ↑WT1 | |
| 9 | 79/M | PMF | JAK2 V617F | HC | 3 | Mk 2 y pre-AML | Wild-type | ND | CBL L380P | ↑WT1 | |
| 10 | 75/F | PV | JAK2 V617F | HC | 12 | None | Wild-type | ND | FLT3-ITD, RUNX1 Q127X | NS | |
| 11 | 64/F | PV | JAK2 V617F | HC | 14 | Blood 1 y pre-AML | Wild-type | ND | TP53 S90X | NS | |
| 12 | 76/M | RARS-T | JAK2 V617F | HC | 8 | None | Wild-type | Complex† | TP53 V173M | ↑WT1 | |
| 13 | 67/M | PV | JAK2 V617F | BU, P32, HC | 26 | Blood 1 y pre-AML | Wild-type | ND | TP53 C238F | ↑WT1 | |
| 14 | 65/M | PV | JAK2 V617F | HC | 10 | Blood 2 y pre-AML | Wild-type | Complex‡ | — | ↑WT1 | |
| 15 | 58/F | PV | JAK2 V617F | HC | 3 | Grans 2 y pre-AML | Wild-type | add(9) | TET2 P1549X | — | |
| 16 | 76/F | ET | JAK2 V617F | HC, BU | 10 | Blood 0.5 y pre-AML | Wild-type | ND | — | NS | |
| Pt . | Myeloproliferative neoplasm . | At transformation to AML . | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age at diagnosis, y/sex . | MPN . | JAK2 mutation status . | Therapy . | Disease duration, y . | Sample from MPN phase . | JAK2 mutation status . | Cytogenetic analysis . | Additional mutations . | Altered gene expression . | ||
| 1 | 63/M | PMF | JAK2 V617F | HC, AN | 2 | BM at diagnosis | Het | 3 copies AML1* | NRAS G12S, RUNX1 D171N | — | |
| 2 | 47/M | ET->MF | JAK2 V617F | HC | 16 | Grans 1 y pre-AML | Hom | inv(3), del(7) | NRAS G12D | ↑WT1, ↑EVI1 | |
| 3 | 47/F | PV->MF | JAK2 V617F | HC, IFN | 10 | Grans 1 y pre-AML | Hom | ND | RUNX1 N119K | ↑WT1 | |
| 4 | 58/M | PMF | JAK2 V617F | none | 1 | None | Hom | ND | RUNX1 G138V | ↑WT1 | |
| 5 | 70/M | Probable PMF | JAK2 V617F | none | NA | NA | Hom | add(8), del(7q) | RUNX1 D171N | ↑WT1 | |
| 6 | 72/M | PMF | JAK2 V617F | HC | 8 | None | Hom | ND | — | ↑WT1, ↑JAK2 | |
| 7 | 67/M | ET->MF | JAK2 V617F | HC | 6 | Grans 1.5 y pre-AML | Hom | der5, t(5;17) | TP53 R248Q | ↑WT1 | |
| 8 | 43/M | PV | JAK2 N542-E543del | BU, P32, HC | 26 | None | Wild-type | del(20q) | TET2 D1242V, RUNX1 H215X | ↑WT1 | |
| 9 | 79/M | PMF | JAK2 V617F | HC | 3 | Mk 2 y pre-AML | Wild-type | ND | CBL L380P | ↑WT1 | |
| 10 | 75/F | PV | JAK2 V617F | HC | 12 | None | Wild-type | ND | FLT3-ITD, RUNX1 Q127X | NS | |
| 11 | 64/F | PV | JAK2 V617F | HC | 14 | Blood 1 y pre-AML | Wild-type | ND | TP53 S90X | NS | |
| 12 | 76/M | RARS-T | JAK2 V617F | HC | 8 | None | Wild-type | Complex† | TP53 V173M | ↑WT1 | |
| 13 | 67/M | PV | JAK2 V617F | BU, P32, HC | 26 | Blood 1 y pre-AML | Wild-type | ND | TP53 C238F | ↑WT1 | |
| 14 | 65/M | PV | JAK2 V617F | HC | 10 | Blood 2 y pre-AML | Wild-type | Complex‡ | — | ↑WT1 | |
| 15 | 58/F | PV | JAK2 V617F | HC | 3 | Grans 2 y pre-AML | Wild-type | add(9) | TET2 P1549X | — | |
| 16 | 76/F | ET | JAK2 V617F | HC, BU | 10 | Blood 0.5 y pre-AML | Wild-type | ND | — | NS | |
Pt indicates patient number; MPN, myeloproliferative neoplasm; PMF, primary myelofibrosis; HC, hydroxycarbamide; AN, anagrelide; BM, bone marrow; het, heterozygous; AML, acute myeloid leukemia; ET, essential thrombocythemia; MF, myelofibrotic transformation; hom, homozygous; PV, polycythemia vera; IFN, interferon-α; ND, not done; NA, not applicable; Grans, granulocytes; BU, busulphan; P32, radioactive phosphorus; Mk, megakaryocytes; NS, no sample available; and RARS-T, refractory anemia with ringed sideroblasts and thrombocytosis.
Detected by fluorescence in situ hybridization; G-banding failed.
43,XY,del(5)(q1q3),−7,−12,−16 [5],43,idem,del(6)(q1q2) [3],46,XY [2].
45-46,XY,del(5)(q1?),add(16)(q2?),−17,−17,−22, +2∼3 mar [10].