Table 1.
Genetic and clinical characteristics of the 12 patients with myeoid malignancies carrying putative somatic UBA1 variants.
| Patient_ID | Age | Sex | Diagnosis | UBA1 Variant | VAF [%] | Vacuole | Co-mutation | Karyotype | Hematological history (age) | Possible immunodysregulation (age) |
|---|---|---|---|---|---|---|---|---|---|---|
| P1 | 77 | male | aCML | M41L | 12 | NA | NRAS (12%) | 46,XY[20] | clinically diagnosed with CML (65); CML diagnosis revised to aCML due to negative BCR::ABL1 [*](75); splenomegaly (circa 40 cm) | none recorded |
| P2 | 82 | male | MDS-MLD | M41T | 76 | NA | none | 46,XY[20] | ESA/transfusion-requring anemia | none recorded |
| P3 | 76 | male | MSD-RS-SLD | M41T | 11 | yes | SF3B1 (31%), JAK2 (14%), ZRSR2 (4%) | 46,XY[20] | thrombocytosis | none recorded |
| P4 | 50 | male | MDS-MLD | M41T | 80 | NA | none | 46,XY,t(2;11)(p21;q23)[13]/46,XY [7] | NA | unspecified autoimmune disease under immunosuppresion |
| P5 | 84 | male | MDS-MLD | M41V | 55 | yes | none | 46,XY,der(1)t(1;2)(p34;q24),der(2)t(1;2)(p36;q24)[7]/46,idem,del5(q14q34)[3]/46,XY[10] | transfusion-requring anemia, pancytopenia | polyneuropathy, latent hyperthyroidism |
| P6 | 76 | male | MDS-RS-MLD | Y55H | 41 | yes | SRSF2 (50%) | 46,XY[20] | [*]MGUS; pancytopenia; anemia treated with 30 mg prednisone/transfusion, successfully discontinued (79) | none recorded |
| I894F | 37 | |||||||||
| P7 | 66 | male | CLL | R182H | 0 | yes | 46,XY, del(11)(q21q23)[4]/46,XY[16] | [*]CLL treated with fludarabine, cyclophosphamide, rituximab (64-65) in CR (66); pancytopenia(65); treated with azacitidine (66) | Pneumocystis pneumonia (65/66), CMV reactivation (65/66) | |
| t-MDS/MDS-EB2 | 57 | NRAS (35%), TP53 (98%) | 44,XY,der(3;21)(q10;q10),-7[20] | |||||||
| P8 | 68 | male | MDS-MLD | A478S | 53 | NA | none | 45,X,-Y [18]/46,XY[2] | primary cutaneous large cell anaplastic T cell lymphoma in the head and neck treated with resection [*] and radiation (68-70); MDS no treatment until age 70 | hyperthyroidism |
| P9 | 69 | male | CML | E597A | 0 | NA | BCR::ABL1 (IS 0.034) | 46,XY,t(7;18)(q11,q23)[7]/46,XY[2] | ET (61) treated with anagrelide; CML [*1] treated with imatinib (67); anemia due to secondary MF (69); transfusion-dependent Coombs-positive anemia (69); 12% blasts with increased borderline monocyte/blasts in PB [*2] (69) | monoblast infiltration in the skin (69), steroid-resistant fever (69) |
| MPN | 75 | NRAS (50%), BCR::ABL1 (IS 0.006) | 46,XY,t(7;18)(q11,q23)[20] | |||||||
| P10 | 67 | male | MDS-RS-MLD | S621C | 90 | yes | FLT3-ITD (39%), RUNX1 (69%), SRSF2 (39%) | 47,XY, + 21[19]/46,XY[1] | steroid-treated hemolytic anemia[*] (67); 9 cycles of azacitidine against MDS (67); decitabine switch (68), 33% blasts in PB, suggesting secondary AML (68); transfusion-dependent anemia | azacitidine injection site reaction (67), antibiotic-resistant broncoscopy-negative pulmonary infiltrate post fungal infection (68) |
| P11 | 73 | male | MDS-MLD | P749L | 10 | NA | none | 47,XX, + X[20] | chronic hemolytic anemia requiring ESA/transfusion | hyperthyroidism treated with nuclear medicine (74) |
| P12 | 63 | male | MDS-RS-SLD | P1014L/canonical splice site | 7 | NA | SF3B1 (49%), TET2 (16%) | 46,XY[20] | autoimmune anemia treated with steroids (62-, tapered and reinitiated), azathioprine[*] (62–63), mycophenol-mofetil (63–74), and rituximab (63, 74), ESA/multiple transfusion (62-) | anti-parietal cell antibody positive gastritis with polyclonal hypergammaglobulinemia and elevated complements (56), IgG4-associated nephritis (58/histology 68), interstitial pneumotitis (62), leiomyosarcoma (71), diverse skin tumors (74) |
[*] indicates the time point the sequencing was performed.
MDS-MLD MDS with multi-lineage dysplasia, MDS-RS-MLD MDS with ring sideroblasts and multi-lineage dysplasia, CLL chronic lymphocytic leukemia, t-MDS therapy-related MDS, MDS-EB MDS with excess blast, CML chronic myeloid leukemia, MPN myeloproliferative neoplasms, MDS-RS-SLD MDS with ring sideroblasts and single-lineage dysplasia, aCML atypical CML, ESA Erythropoiesis-stimulating agent, NA not available, MGUS monoclonal gammopathy of undetermined significance, CR complete remission, ET essential thrombocythemia, MF myelofibrosis, PB peripheral blood, AML acute myeloid leukemia.