Characteristics of UBA1-mutated patients
| Patient ID . | #UPN1 . | #UPN2 . | #UPN3 . | #UPN4 . | #UPN5 . | #UPN6 . |
|---|---|---|---|---|---|---|
| Sex | M | M | M | M | M | M |
| Age at onset (years) | 43 | 56 | 63 | 48 | 56 | 50 |
| UBA1 mutation | c.121A>G, p.Met41Val (VAF 73%) | c.121A>G, p.Met41Val (VAF 88%) | c.121A>C, p.Met41Leu (VAF 43%) | c.122T>C, p.Met41Thr (VAF 67%) | c.121A>G, p.Met41Val (VAF: NA)‡ | c.121A>G, p.Met41Val (VAF: NA)‡ |
| Key clinical features | ||||||
| Neutrophilic dermatosis | + | + | + | + | — | — |
| Polyarteritis nodosa | + | — | + | — | — | — |
| Chondritis | — | — | + | + | + | + |
| Pulmonary involvement | — | — | — | + | + | — |
| Deep vein thrombosis | — | — | — | + | — | — |
| Laboratory findings* | ||||||
| Hemoglobin concentration (g/l) | 96 | 92 | 102 | 78 | 110 | 131 |
| Mean corpuscular volume (fl) | 102 | 98 | 104 | 105 | 91.2 | 113.7 |
| Platelet count (×10^9/l) | 225 | 67 | 157 | 341 | 268 | 153 |
| Neutrophil count (10^9/l) | 2.1 | 11.8 | 4.0 | 4.6 | 5.5 | 1.2 |
| Bone marrow vacuoles | + | + | + | + | NA | NA |
| Additional genetic aberrations (HTS and cytogenetics) | Normal karyotype No additional mutation | Normal karyotype DNMT3A p.Trp795Ser (VAF 43%)†RUNX1 p.Gly165fs (VAF 2%) | Normal karyotype CBL c.1228-2A>G (VAF 9%) KRAS p.Gly12Arg (VAF 2%) NRAS p.Tyr64Asp (VAF 1%) TET2 p.Leu1622Ter (VAF 49%) TET2 p.Lys1317Ter (VAF 2%) ZRSR2 p.Arg27fs (VAF 4%) | Normal karyotype No additional mutation | Normal karyotype TET2 p.Thr1554fs (VAF 3%) | Trisomy 8 No additional mutation |
| Hematologic diseases | ||||||
| Myelodysplastic syndrome | + | — | + | + | + | + |
| Myelofibrosis | — | + | — | — | + | |
| Number of prior lines of therapy | 6 | 8 | 7 | 6 | 5 | 4 |
| GC, anakinra, dapsone, canakinumab, AZA, HCQ | GC, CP, IVIG, rituximab, danazol, anakinra, dapsone, canakinumab | GC, MTX, anakinra, canakinumab, tocilizumab, IVIG, 5-AZA | GC, dapsone, colchicine, anakinra, canakinumab, siltuximab | GC, tocilizumab, adalimumab, 5-AZA, ruxolitinib | GC, MMF, colchicine, 5-AZA | |
| Reaction at anakinra injection | — | — | + | + | NA | NA |
| Allogeneic HSCT | ||||||
| Age at time of HSCT | 46 | 59 | 65 | 50 | 58 | 55 |
| Conditioning | fludarabine, busulfan, ATG | fludarabine, busulfan | fludarabine, busulfan | fludarabine, busulfan, ATG | fludarabine, busulfan, thiotepa | busulfan, CPA, ATG |
| Donor | Unrelated donor Pheno-identical 10/10 | Related donor | Unrelated donor Pheno-identical 10/10 | Unrelated donor Pheno-identical 10/10 | Related donor | Unrelated donor Pheno-identical 10/10 |
| Graft origin | Peripheral blood | Bone marrow | Peripheral blood | Peripheral blood | Peripheral blood | Peripheral blood |
| GVH prophylaxis | CSA, MMF | CSA, MTX | CSA, MMF, CP | CSA, MTX | CSA, MMF, CP | CSA, MTX |
| Infectious complications | None | None | E. coli bacteremia, BK virus-related hemorrhagic cystitis, CMV replication | Bacterial catheter related infection | Bacterial catheter related infection | Bacterial catheter related infection, fusariosis |
| Immune complications | Chronic cutaneous GVHD, hepatic GHVD | Chronic cutaneous GVHD | Acute cutaneous GVHD grade I | None | Acute gastrointestinal GVHD grade II Cutaneous GVHD grade I | Acute gastrointestinal GVHD grade III |
| Clinical response | CR | CR | CR | CR | CR | Death prior evaluation |
| Follow-up (months) | 32 | 67 | 38 | 3 | 5 | 4 |
| Alive at end of follow-up | + | + | + | + | + | — |
| Patient ID . | #UPN1 . | #UPN2 . | #UPN3 . | #UPN4 . | #UPN5 . | #UPN6 . |
|---|---|---|---|---|---|---|
| Sex | M | M | M | M | M | M |
| Age at onset (years) | 43 | 56 | 63 | 48 | 56 | 50 |
| UBA1 mutation | c.121A>G, p.Met41Val (VAF 73%) | c.121A>G, p.Met41Val (VAF 88%) | c.121A>C, p.Met41Leu (VAF 43%) | c.122T>C, p.Met41Thr (VAF 67%) | c.121A>G, p.Met41Val (VAF: NA)‡ | c.121A>G, p.Met41Val (VAF: NA)‡ |
| Key clinical features | ||||||
| Neutrophilic dermatosis | + | + | + | + | — | — |
| Polyarteritis nodosa | + | — | + | — | — | — |
| Chondritis | — | — | + | + | + | + |
| Pulmonary involvement | — | — | — | + | + | — |
| Deep vein thrombosis | — | — | — | + | — | — |
| Laboratory findings* | ||||||
| Hemoglobin concentration (g/l) | 96 | 92 | 102 | 78 | 110 | 131 |
| Mean corpuscular volume (fl) | 102 | 98 | 104 | 105 | 91.2 | 113.7 |
| Platelet count (×10^9/l) | 225 | 67 | 157 | 341 | 268 | 153 |
| Neutrophil count (10^9/l) | 2.1 | 11.8 | 4.0 | 4.6 | 5.5 | 1.2 |
| Bone marrow vacuoles | + | + | + | + | NA | NA |
| Additional genetic aberrations (HTS and cytogenetics) | Normal karyotype No additional mutation | Normal karyotype DNMT3A p.Trp795Ser (VAF 43%)†RUNX1 p.Gly165fs (VAF 2%) | Normal karyotype CBL c.1228-2A>G (VAF 9%) KRAS p.Gly12Arg (VAF 2%) NRAS p.Tyr64Asp (VAF 1%) TET2 p.Leu1622Ter (VAF 49%) TET2 p.Lys1317Ter (VAF 2%) ZRSR2 p.Arg27fs (VAF 4%) | Normal karyotype No additional mutation | Normal karyotype TET2 p.Thr1554fs (VAF 3%) | Trisomy 8 No additional mutation |
| Hematologic diseases | ||||||
| Myelodysplastic syndrome | + | — | + | + | + | + |
| Myelofibrosis | — | + | — | — | + | |
| Number of prior lines of therapy | 6 | 8 | 7 | 6 | 5 | 4 |
| GC, anakinra, dapsone, canakinumab, AZA, HCQ | GC, CP, IVIG, rituximab, danazol, anakinra, dapsone, canakinumab | GC, MTX, anakinra, canakinumab, tocilizumab, IVIG, 5-AZA | GC, dapsone, colchicine, anakinra, canakinumab, siltuximab | GC, tocilizumab, adalimumab, 5-AZA, ruxolitinib | GC, MMF, colchicine, 5-AZA | |
| Reaction at anakinra injection | — | — | + | + | NA | NA |
| Allogeneic HSCT | ||||||
| Age at time of HSCT | 46 | 59 | 65 | 50 | 58 | 55 |
| Conditioning | fludarabine, busulfan, ATG | fludarabine, busulfan | fludarabine, busulfan | fludarabine, busulfan, ATG | fludarabine, busulfan, thiotepa | busulfan, CPA, ATG |
| Donor | Unrelated donor Pheno-identical 10/10 | Related donor | Unrelated donor Pheno-identical 10/10 | Unrelated donor Pheno-identical 10/10 | Related donor | Unrelated donor Pheno-identical 10/10 |
| Graft origin | Peripheral blood | Bone marrow | Peripheral blood | Peripheral blood | Peripheral blood | Peripheral blood |
| GVH prophylaxis | CSA, MMF | CSA, MTX | CSA, MMF, CP | CSA, MTX | CSA, MMF, CP | CSA, MTX |
| Infectious complications | None | None | E. coli bacteremia, BK virus-related hemorrhagic cystitis, CMV replication | Bacterial catheter related infection | Bacterial catheter related infection | Bacterial catheter related infection, fusariosis |
| Immune complications | Chronic cutaneous GVHD, hepatic GHVD | Chronic cutaneous GVHD | Acute cutaneous GVHD grade I | None | Acute gastrointestinal GVHD grade II Cutaneous GVHD grade I | Acute gastrointestinal GVHD grade III |
| Clinical response | CR | CR | CR | CR | CR | Death prior evaluation |
| Follow-up (months) | 32 | 67 | 38 | 3 | 5 | 4 |
| Alive at end of follow-up | + | + | + | + | + | — |
5-AZA, 5-azacytidine, ATG, antithymocyte globulin; AZA, azathioprine; CP, cyclophosphamide; CR, complete remission; CSA, cyclosporine; GC, glucocorticoid; GVHD, graft-versus-host disease; HCQ, hydroxychloroquine; HSCT, hematopoietic stem cell transplantation; IVIG, intravenous immunoglobulin; M, male; MMF, mycophenolate mofetil; MTX, methotrexate; NA, not applicable; VAF, variant allele frequency.
At time of first bone marrow examination.
The somatic state of the DNMT3A mutation was confirmed by sequencing on a skin biopsy.
Sanger sequencing only.