GATA1 mutations in TMD/AMKL patients with multiple samples
Pt and diagnosis . | Sex . | Age at diagnosis (mo) . | DNA source . | WBC count, × 109/L (% blast) . | Karyotype . | Sequence in genomic DNA*† . | Cloned sequence from genomic DNA (no. mutant clones/no. total clones)† . | Radiolabeled GATA1 exon 2 PCR products . | Cloned sequence of bands cut from gels (no. mutant clones/no. total clones)† . | Consequence of mutation† . | Clinical status/time since diagnosis . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| L12 | F | CCR/48 mo | |||||||||
| Normal | Birth | BG | — | ND | Wild type | Wild type (0/6) | Wild-type band and faint deletion band | 269 del 23 (5/10) | 269 del 23 - Stop codon before Met 84 | ||
| AMKL | 13 | Diagnosis BM | 8.3 (44) | 48,XX,del (6) (q?13q? 21), +21c,+21[5] | 269 del 23 | 269 del 23 (3/15) | Wild-type band and prominent deletion band 1; faint deletion band 1 | 269 del 23 (8/15); NA | 269 del 23 - Stop codon before Met 84 | ||
| 48, idem, dup (1) (q? 31q 42)[6] | |||||||||||
| 47, XX, +21c[6] | |||||||||||
| Remission | — | CR BM | (3) | 47, XX, +21c[11] | Wild type | ND | Wild-type band | ND | No mutation detected | ||
| L13 | M | CCR/51 mo | |||||||||
| Normal | Birth | BG | — | ND | Wild type | Wild type (0/12) | Wild-type band and faint deletion band 1 | 273 del 17 (1/6) | 273 del 17 - Stop codon before Met 84 | ||
| AMKL | 26 | Diagnosis BM | 3.95 (39) | 47,XY,21+(c)del(6)(?q) [4] | 273 del 17 | ND | Wild-type band and prominent deletion band 1; faint deletion band 1; faint deletion band 2 | 273 del 17 (4/4); NA; NA | 273 del 17 - Stop codon before Met 84 | ||
| 47,XY,21 +(c) in [12] | |||||||||||
| Remission | CR BM | (2) | 47, XY, +21(c)[14] | Wild type | ND | Wild-type band | ND | No mutation detected | |||
| L14 | F | CCR/60 mo | |||||||||
| TMD | Birth | PB smear | 58 (50) | 47, XY, +21(c) | 235 del 132 | 235 del 132 (3/6) | Wild-type band and prominent deletion band | 235 del 132 (3/9) | 235 del 132 - Exon 2 splice mutant | ||
| AMKL | 21 | Diagnosis BM | 5.4 (46) | Hyperdiploid 52 chromosomes | 235 del 132 | 235 del 132 (3/20) | Wild-type band and prominent deletion band | ND | 235 del 132 - Exon 2 splice mutant | ||
| 52 XX, +21(c), +11, +13,+19,+21, +X[2] | |||||||||||
| 52 idem, der3t(1:3)(2?;p2.6) [2] | |||||||||||
| Remission | CR BM | (4) | 47, XX, +21c[8] | Wild type | ND | Wild-type band | ND | No mutation detected | |||
| L15 | M | CCR/4 mo | |||||||||
| Normal | Birth | BG | — | ND | 202 del 2 | 202 del 2 (9/28); 262 ins 1 (2/28); 331A>G (2/28) | Wild-type band | ND | 202 del 2 - Stop codon before Met84; 262 ins 1 - Stop codon before Met 84; 331A>G - Exon 2 splice mutant | ||
| AMKL | 12 | Diagnosis BM | 7.3 (50) | 50,XY,+19,+21c,+21,+22[6] | 202 del 2 | 202 del 2 (6/27) | Wild-type band | ND | 202 del 2 - Stop codon before Met 84 | ||
| 47,XY,+21c[13] | |||||||||||
| Remission | CR BM | (<5) | 47,XY,+21c[10] | Wild type | ND | Wild-type band | ND | No mutation detected | |||
| L17 | M | CCR/42 mo | |||||||||
| Normal | Birth | BG | — | ND | Wild type | Wild type (0/58) | Wild-type band | ND | No mutation detected | ||
| MDS/AMKL | 22 | Diagnosis BM | 7.7 (27) | 48,XY,dup(3) (q2? 5q2? 6.2), der (10) | 332G>A | 332G>A (7/15) | Wild-type band | ND | 332G>A - Exon 2 splice mutant | ||
| t(1:10)(q21;q26), +21c,+21[11] 47,XY,+21c[2] | |||||||||||
| Remission | CR BM | (4) | 47, XX, +21c[11] | Wild type | ND | Wild-type band | ND | No mutation detected | |||
| L16 | M | 2 mo into treatment | |||||||||
| AMKL | 1 | Diagnosis BM | 23.1 (50) | 47,XY,+21c[14] | 161 C>T | 161 C>T(2/10) | Wild-type band | 161 C>T(2/4) | 161 C>T - Stop codon before Met 84 | ||
| Remission | Post-Rx BM | (2) | ND | Wild type | ND | Wild-type band | ND | No mutation detected | |||
| T01 | F | Alive and well at 30 mo | |||||||||
| TMD | Birth | PB smear | 80 (50) | 47, XX, +21(c)[7] | 286 ins 16 (dup270-285) | ND | Wild-type band and insertion band 1 | 286 ins 16 (dup270-285) (5/7) | 286 ins 16 (dup 270-285) - Stop codon before Met 84 | ||
| Remission | 18 | CR PB | 8.6 (0) | ND | Wild type | ND | Wild-type band | ND | No mutation detected | ||
| T02 | M | CCR/85 mo | |||||||||
| TMD | 10 days | PB smear | 250 (44) | 47, XY, +21(c) Mosaic Down[3] | 235 del 132 | 235 del 132 (13/15) | Wild-type band and prominent deletion band | 235 del 132 (3/5) | 235 del 132 - Exon 2 splice mutant | ||
| Remission | 84 | PB | 4.8 (0) | ND | Wild type | ND | Wild-type band | ND | No mutation detected |
Pt and diagnosis . | Sex . | Age at diagnosis (mo) . | DNA source . | WBC count, × 109/L (% blast) . | Karyotype . | Sequence in genomic DNA*† . | Cloned sequence from genomic DNA (no. mutant clones/no. total clones)† . | Radiolabeled GATA1 exon 2 PCR products . | Cloned sequence of bands cut from gels (no. mutant clones/no. total clones)† . | Consequence of mutation† . | Clinical status/time since diagnosis . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| L12 | F | CCR/48 mo | |||||||||
| Normal | Birth | BG | — | ND | Wild type | Wild type (0/6) | Wild-type band and faint deletion band | 269 del 23 (5/10) | 269 del 23 - Stop codon before Met 84 | ||
| AMKL | 13 | Diagnosis BM | 8.3 (44) | 48,XX,del (6) (q?13q? 21), +21c,+21[5] | 269 del 23 | 269 del 23 (3/15) | Wild-type band and prominent deletion band 1; faint deletion band 1 | 269 del 23 (8/15); NA | 269 del 23 - Stop codon before Met 84 | ||
| 48, idem, dup (1) (q? 31q 42)[6] | |||||||||||
| 47, XX, +21c[6] | |||||||||||
| Remission | — | CR BM | (3) | 47, XX, +21c[11] | Wild type | ND | Wild-type band | ND | No mutation detected | ||
| L13 | M | CCR/51 mo | |||||||||
| Normal | Birth | BG | — | ND | Wild type | Wild type (0/12) | Wild-type band and faint deletion band 1 | 273 del 17 (1/6) | 273 del 17 - Stop codon before Met 84 | ||
| AMKL | 26 | Diagnosis BM | 3.95 (39) | 47,XY,21+(c)del(6)(?q) [4] | 273 del 17 | ND | Wild-type band and prominent deletion band 1; faint deletion band 1; faint deletion band 2 | 273 del 17 (4/4); NA; NA | 273 del 17 - Stop codon before Met 84 | ||
| 47,XY,21 +(c) in [12] | |||||||||||
| Remission | CR BM | (2) | 47, XY, +21(c)[14] | Wild type | ND | Wild-type band | ND | No mutation detected | |||
| L14 | F | CCR/60 mo | |||||||||
| TMD | Birth | PB smear | 58 (50) | 47, XY, +21(c) | 235 del 132 | 235 del 132 (3/6) | Wild-type band and prominent deletion band | 235 del 132 (3/9) | 235 del 132 - Exon 2 splice mutant | ||
| AMKL | 21 | Diagnosis BM | 5.4 (46) | Hyperdiploid 52 chromosomes | 235 del 132 | 235 del 132 (3/20) | Wild-type band and prominent deletion band | ND | 235 del 132 - Exon 2 splice mutant | ||
| 52 XX, +21(c), +11, +13,+19,+21, +X[2] | |||||||||||
| 52 idem, der3t(1:3)(2?;p2.6) [2] | |||||||||||
| Remission | CR BM | (4) | 47, XX, +21c[8] | Wild type | ND | Wild-type band | ND | No mutation detected | |||
| L15 | M | CCR/4 mo | |||||||||
| Normal | Birth | BG | — | ND | 202 del 2 | 202 del 2 (9/28); 262 ins 1 (2/28); 331A>G (2/28) | Wild-type band | ND | 202 del 2 - Stop codon before Met84; 262 ins 1 - Stop codon before Met 84; 331A>G - Exon 2 splice mutant | ||
| AMKL | 12 | Diagnosis BM | 7.3 (50) | 50,XY,+19,+21c,+21,+22[6] | 202 del 2 | 202 del 2 (6/27) | Wild-type band | ND | 202 del 2 - Stop codon before Met 84 | ||
| 47,XY,+21c[13] | |||||||||||
| Remission | CR BM | (<5) | 47,XY,+21c[10] | Wild type | ND | Wild-type band | ND | No mutation detected | |||
| L17 | M | CCR/42 mo | |||||||||
| Normal | Birth | BG | — | ND | Wild type | Wild type (0/58) | Wild-type band | ND | No mutation detected | ||
| MDS/AMKL | 22 | Diagnosis BM | 7.7 (27) | 48,XY,dup(3) (q2? 5q2? 6.2), der (10) | 332G>A | 332G>A (7/15) | Wild-type band | ND | 332G>A - Exon 2 splice mutant | ||
| t(1:10)(q21;q26), +21c,+21[11] 47,XY,+21c[2] | |||||||||||
| Remission | CR BM | (4) | 47, XX, +21c[11] | Wild type | ND | Wild-type band | ND | No mutation detected | |||
| L16 | M | 2 mo into treatment | |||||||||
| AMKL | 1 | Diagnosis BM | 23.1 (50) | 47,XY,+21c[14] | 161 C>T | 161 C>T(2/10) | Wild-type band | 161 C>T(2/4) | 161 C>T - Stop codon before Met 84 | ||
| Remission | Post-Rx BM | (2) | ND | Wild type | ND | Wild-type band | ND | No mutation detected | |||
| T01 | F | Alive and well at 30 mo | |||||||||
| TMD | Birth | PB smear | 80 (50) | 47, XX, +21(c)[7] | 286 ins 16 (dup270-285) | ND | Wild-type band and insertion band 1 | 286 ins 16 (dup270-285) (5/7) | 286 ins 16 (dup 270-285) - Stop codon before Met 84 | ||
| Remission | 18 | CR PB | 8.6 (0) | ND | Wild type | ND | Wild-type band | ND | No mutation detected | ||
| T02 | M | CCR/85 mo | |||||||||
| TMD | 10 days | PB smear | 250 (44) | 47, XY, +21(c) Mosaic Down[3] | 235 del 132 | 235 del 132 (13/15) | Wild-type band and prominent deletion band | 235 del 132 (3/5) | 235 del 132 - Exon 2 splice mutant | ||
| Remission | 84 | PB | 4.8 (0) | ND | Wild type | ND | Wild-type band | ND | No mutation detected |
BG indicates Birth Guthrie DNA (neonatal blood spot) sample; PB, peripheral blood sample; BM, bone marrow; Post-Rx, after treatment; CR, complete remission; CCR, complete continuous remission; ND, not done; NA, not available.
Sequence obtained from direct sequencing of genomic DNA