Characteristics of patients with FPD who progressed to acute leukemia and types of RUNX1 gene alterations
| Pedigree/patient . | Age at AL diagnosis, y . | Sex . | Type of AL . | Karyotype at AL stage . | Germline RUNX1 alteration . | Acquired RUNX1 alteration at AL stage . | Loss of the acquired RUNX1 alteration in CR . | Biallelic RUNX1 mutations . | Other gene mutations detected . | Relapse . | ABMT with related donor* (donor) . | Status at last follow-up . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1/III:2 | 25 | M | AML-M5 | ND | p.Ala129Glu mutation | p.Glu395_Arg400>HisfsX172 mutation | ND | ND | None | Yes† (after ABMT) | Yes (brother III:5) | Death |
| 1/III:4 | 25 | M | AML-M5 | ND | p.Ala129Glu mutation | p.Arg135Ser mutation | ND | Yes | None | NA (refractory disease) | No | Death |
| 1/III:6 | 42 | F | AML-M0 | 46,XX, +21[14] | p.Ala129Glu mutation | Duplication of the chromosome carrying the mutated allele | ND | NA | None | Yes‡ | No | Death |
| 2/II:3 | 60 | M | AML-M4 | 46,XY [20] | p.Arg177Gln mutation | p.Ala160Thr mutation | Yes | Yes | FLT3-ITD | No | No | Alive in CR |
| 2/III:1 | 28 | M | T-ALL | 46,XY [20] | p.Arg177Gln mutation | Absence | NA | NA | None | No | Yes (sister III:2) | Alive in CR |
| 3/I:2 | 55 | F | AML-M5 | 46,XX [20] | p.Gln308ArgfsX259 mutation | p.Gly138ProfsX12 mutation | Yes | ND | None | No | Yes (sister) | Alive in CR |
| 3/II:2 | 24 | F | AML-M2§ | 46,XX,t(1;3)(p36;q26)[15]/46,XX[5] | p.Gln308ArgfsX259 mutation | Absence | NA | NA | K-RAS mutation (p.Gly12Asp) | No | No | Death |
| 4/I:1 | 12 | F | AML-M6 | 48,XXXc,+21[28]/47,XXXc[3] | Complete deletion of RUNX1 gene | Duplication of the chromosome carrying the deleted allele | Yes | NA | None | Yes†‖ (after ABMT) | Yes (sister) | Alive in relapse |
| Pedigree/patient . | Age at AL diagnosis, y . | Sex . | Type of AL . | Karyotype at AL stage . | Germline RUNX1 alteration . | Acquired RUNX1 alteration at AL stage . | Loss of the acquired RUNX1 alteration in CR . | Biallelic RUNX1 mutations . | Other gene mutations detected . | Relapse . | ABMT with related donor* (donor) . | Status at last follow-up . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1/III:2 | 25 | M | AML-M5 | ND | p.Ala129Glu mutation | p.Glu395_Arg400>HisfsX172 mutation | ND | ND | None | Yes† (after ABMT) | Yes (brother III:5) | Death |
| 1/III:4 | 25 | M | AML-M5 | ND | p.Ala129Glu mutation | p.Arg135Ser mutation | ND | Yes | None | NA (refractory disease) | No | Death |
| 1/III:6 | 42 | F | AML-M0 | 46,XX, +21[14] | p.Ala129Glu mutation | Duplication of the chromosome carrying the mutated allele | ND | NA | None | Yes‡ | No | Death |
| 2/II:3 | 60 | M | AML-M4 | 46,XY [20] | p.Arg177Gln mutation | p.Ala160Thr mutation | Yes | Yes | FLT3-ITD | No | No | Alive in CR |
| 2/III:1 | 28 | M | T-ALL | 46,XY [20] | p.Arg177Gln mutation | Absence | NA | NA | None | No | Yes (sister III:2) | Alive in CR |
| 3/I:2 | 55 | F | AML-M5 | 46,XX [20] | p.Gln308ArgfsX259 mutation | p.Gly138ProfsX12 mutation | Yes | ND | None | No | Yes (sister) | Alive in CR |
| 3/II:2 | 24 | F | AML-M2§ | 46,XX,t(1;3)(p36;q26)[15]/46,XX[5] | p.Gln308ArgfsX259 mutation | Absence | NA | NA | K-RAS mutation (p.Gly12Asp) | No | No | Death |
| 4/I:1 | 12 | F | AML-M6 | 48,XXXc,+21[28]/47,XXXc[3] | Complete deletion of RUNX1 gene | Duplication of the chromosome carrying the deleted allele | Yes | NA | None | Yes†‖ (after ABMT) | Yes (sister) | Alive in relapse |
AL indicates acute leukemia; AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; FPD, familial platelet disorder; ITD, internal tandem duplication; ND, not determined; NA, not applicable; ABMT, allogeneic bone marrow transplantation; and CR, complete remission.
The HLA-matched related donor of each patient who underwent ABMT was screened for RUNX1 alterations and was found to have a wild-type status.
RUNX1 status identical at diagnosis and at relapse.
RUNX1 mutations could not be tested at relapse.
AML after T-ALL was probably therapy related.
Complex cytogenetic aberrations and FLT3-ITD mutation acquired at relapse.