Fanconi anemia patients with reversion (somatic mosaicism)
. | . | . | PBL breaks . | . | . | . | . | . | . | . | . | . | . | . | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | . | . | 0 . | . | 1 . | . | ≥ 2 . | . | . | FANCD2 test . | . | . | . | . | ||||||
| Patient no. . | Age, y . | Group . | NM– . | NM+ . | NM– . | NM+ . | NM– . | NM+ . | Result . | PBL . | Fibro . | Breaks, fibro . | Follow-up, y . | Comments . | ||||||
| EGFA012 | 6 | A | 46 | 27 | 3 | 2 | 1 | 21* | POS | 2 | 1 | ND | 4 | FA reversion in a fraction of PBLs | ||||||
| Mild pancytopenia with recent improvement | ||||||||||||||||||||
| EGFA013 | 21 | A | 47 | 40 | 2 | 0 | 1 | 10* | POS | 2 | 1 | ND | 13 | FA reversion in a fraction of PBLs | ||||||
| Normal blood cell counts since diagnosis 13 years before ps | ||||||||||||||||||||
| Dysplasia in mouth | ||||||||||||||||||||
| EGFA039 | 10 | A | 44 | 22 | 5 | 6 | 1 | 22* | POS | 2 | 1 | ND | 1 | FA reversion in a fraction of PBLs | ||||||
| New diagnosis | ||||||||||||||||||||
| Thrombocytopenia; normal WBC and Hb | ||||||||||||||||||||
| EGFA050 | 4 | D2 | 49 | 37 | 1 | 4 | 0 | 9* | POS | 2 | 0 | ND | 4 | FA reversion in a fraction of PBLs | ||||||
| Normal blood cell counts since diagnosis | ||||||||||||||||||||
| EGFA008 | 23 | A | 50 | 46 | 0 | 4 | 0 | 0 | NEG | 2 | 1 | ND | 10 | FA reversion in PBLs (complete) | ||||||
| Mild pancytopenia since diagnosis | ||||||||||||||||||||
| Negative PBL breaks at diagnosis 10 years before ps | ||||||||||||||||||||
| EGFA006 | 8 | Unid | 49 | 48 | 1 | 2 | 0 | 0 | NEG | 2 | 2† | POS | 3 | FA reversion in PBLs (complete) | ||||||
| Persistent mild anemia since diagnosis | ||||||||||||||||||||
| Positive PBL breaks at diagnosis 8 years before ps | ||||||||||||||||||||
| EGFA047 | 34 | A | 49 | 48 | 1 | 1 | 0 | 1 | NEG | 2 | 1 | POS | 27 | FA reversion in PBLs (complete) | ||||||
| Anemia and severe thrombopenia at diagnosis; improvement and subnormal blood counts since 27 years with low-dose androgens (Figure 2) | ||||||||||||||||||||
| Dysplasia in mouth | ||||||||||||||||||||
| EGFA053 | 10 | Unid | 48 | 44 | 2 | 3 | 0 | 3* | AMB | 2 | 2† | POS | 6 | FA reversion in a fraction of PBLs | ||||||
| Mild pancytopenia since diagnosis | ||||||||||||||||||||
| Positive PBL breaks at 10 years before ps | ||||||||||||||||||||
. | . | . | PBL breaks . | . | . | . | . | . | . | . | . | . | . | . | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | . | . | 0 . | . | 1 . | . | ≥ 2 . | . | . | FANCD2 test . | . | . | . | . | ||||||
| Patient no. . | Age, y . | Group . | NM– . | NM+ . | NM– . | NM+ . | NM– . | NM+ . | Result . | PBL . | Fibro . | Breaks, fibro . | Follow-up, y . | Comments . | ||||||
| EGFA012 | 6 | A | 46 | 27 | 3 | 2 | 1 | 21* | POS | 2 | 1 | ND | 4 | FA reversion in a fraction of PBLs | ||||||
| Mild pancytopenia with recent improvement | ||||||||||||||||||||
| EGFA013 | 21 | A | 47 | 40 | 2 | 0 | 1 | 10* | POS | 2 | 1 | ND | 13 | FA reversion in a fraction of PBLs | ||||||
| Normal blood cell counts since diagnosis 13 years before ps | ||||||||||||||||||||
| Dysplasia in mouth | ||||||||||||||||||||
| EGFA039 | 10 | A | 44 | 22 | 5 | 6 | 1 | 22* | POS | 2 | 1 | ND | 1 | FA reversion in a fraction of PBLs | ||||||
| New diagnosis | ||||||||||||||||||||
| Thrombocytopenia; normal WBC and Hb | ||||||||||||||||||||
| EGFA050 | 4 | D2 | 49 | 37 | 1 | 4 | 0 | 9* | POS | 2 | 0 | ND | 4 | FA reversion in a fraction of PBLs | ||||||
| Normal blood cell counts since diagnosis | ||||||||||||||||||||
| EGFA008 | 23 | A | 50 | 46 | 0 | 4 | 0 | 0 | NEG | 2 | 1 | ND | 10 | FA reversion in PBLs (complete) | ||||||
| Mild pancytopenia since diagnosis | ||||||||||||||||||||
| Negative PBL breaks at diagnosis 10 years before ps | ||||||||||||||||||||
| EGFA006 | 8 | Unid | 49 | 48 | 1 | 2 | 0 | 0 | NEG | 2 | 2† | POS | 3 | FA reversion in PBLs (complete) | ||||||
| Persistent mild anemia since diagnosis | ||||||||||||||||||||
| Positive PBL breaks at diagnosis 8 years before ps | ||||||||||||||||||||
| EGFA047 | 34 | A | 49 | 48 | 1 | 1 | 0 | 1 | NEG | 2 | 1 | POS | 27 | FA reversion in PBLs (complete) | ||||||
| Anemia and severe thrombopenia at diagnosis; improvement and subnormal blood counts since 27 years with low-dose androgens (Figure 2) | ||||||||||||||||||||
| Dysplasia in mouth | ||||||||||||||||||||
| EGFA053 | 10 | Unid | 48 | 44 | 2 | 3 | 0 | 3* | AMB | 2 | 2† | POS | 6 | FA reversion in a fraction of PBLs | ||||||
| Mild pancytopenia since diagnosis | ||||||||||||||||||||
| Positive PBL breaks at 10 years before ps | ||||||||||||||||||||
Patients are ordered in this table as presented in the text. Results shown in this table were obtained during the course of the present study (ps). Unid indicates unidentified downstream group(s). Chromosome breakage tests performed with (NM+) and without (NM–) exposure to nitrogen mustard; nos. of mitosis with 0, 1, and ≥ 2 breaks are indicated; conclusions of the chromosomal breakage tests are indicated as POS, positive, NEG, negative, AMB, ambiguous result. FANCD2 tests: 2, both the short and long FANCD2 isoforms were detected using FANCD2 immunoblot; 1, only the FANCD2-S isoform was detected; 0, no FANCD2 protein was detected; †, 2 and 4 independant primary fibroblasts clones were tested in patients EGFA006 and EGFA053, respectively. Breaks fibro : breakage tests in primary fibroblasts; nd, not tested. The association of a positive chromome breakage test which includes a population of resistant cells to the detection of FANCD2 monoubiquitination is consistent with FA reversion present in a fraction of the PBLs. Follow up, years of clinical follow up in our institution (it can be shorter than the time from the diagnosis as indicated in Table 1 since a number of patients were referred in our center years after diagnosis). Partial mosaicism was defined by the persistence of a number of mitosis with multiples breaks (≥ 5 breaks); complete mosaicism was defined by normal breakage tests in PBLs.
Including mitosis with ≥ 5 breaks by mitosis