Frequency of copy number alterations and mutations at the time of marrow relapse in childhood acute lymphoblastic leukemia (ALL) stratified by chromosomal abnormality and cytogenetic risk group
| Copy number alteration/mutation . | Total number of cases . | Overall frequency, %† . | Frequency of copy number alterations and mutations by chromosomal abnormality and cytogenetic risk group . | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cytogenetic risk group . | Chromosomal abnormality . | |||||||||||||||
| Good . | Intermediate . | High . | ETV6-RUNX1 . | High Hyperdiploid . | B‐other . | t(1;19) . | IGH translocation . | KMT2A translocation . | iAMP21 . | Haploid . | Low hypodiploid‡ . | t(17;19) . | t(9;22) . | |||
| Total number of cases tested§ | 238 | 100 | 107 | 80 | 27 | 45 | 66 | 74 | 4 | 7 | 12 | 10 | 4 | 3 | 3 | 2 |
| CDKN2A/B deletion | 90 | 41 | 36%* | 54%* | 30%* | 34% | 37% | 59%** | 25% | 14% | 10%* | 20% | — | 100% | 33% | 100% |
| IKZF1 deletion | 52 | 23 | 11%** | 40%** | 26% | 2%** | 17% | 42%** | 25% | 29% | 20% | 40% | — | 50% | 0% | 0% |
| PAX5 alteration | 44 | 20 | 14% | 28% | 19% | 18% | 11%* | 32%** | 0% | 0% | 20% | 20% | — | 50% | 0% | 0% |
| ETV6 deletion | 36 | 16 | 18% | 11% | 26% | 34%** | 6%* | 10% | 50% | 0% | 0% | 60%** | — | 0% | 0% | 50% |
| TP53 alteration¶ | 29 | 10 | 7% | 7% | 28%** | 5% | 8% | 7% | 17% | 13% | 12% | 27% | 100%** | 40% | 0% | 0% |
| KRAS mutation | 26 | 12 | 11% | 14% | 10% | 0%** | 18% | 14% | 0% | 17% | 18% | 0% | 0% | 0% | 33% | 0% |
| NRAS mutation | 26 | 12 | 15% | 9% | 13% | 3%* | 23%** | 7% | 25% | 17% | 9% | 25% | 25% | 0% | 0% | 0% |
| P2RY8‐CRLF2 | 21 | 10 | 8% | 14% | 7% | 14% | 3%* | 12% | 25% | 29% | 10% | 10% | — | 0% | 0% | 0% |
| NR3C1 deletion | 18 | 9 | 9% | 6% | 22% | 14% | 6% | 7% | 0% | 0% | 18% | 11% | — | 50% | 67%** | 0% |
| PTPN11 mutation | 17 | 8 | 11% | 5% | 0% | 0% | 18%** | 6% | 0% | 0% | 0% | 0% | 0% | 0% | 0% | 0% |
| BTG1 deletion | 11 | 5 | 4% | 6% | 7% | 9% | 0%* | 6% | 0% | 14% | 0% | 0% | — | 50% | 33% | 0% |
| RB1 deletion | 11 | 5 | 3% | 10% | 0% | 2% | 3% | 12%** | 0% | 0% | 0% | 0% | — | 0% | 0% | 0% |
| EBF1 deletion | 10 | 5 | 4% | 6% | 0% | 7% | 2% | 6% | 0% | 14% | 0% | 0% | — | 0% | 0% | 0% |
| FLT3 mutation | 9 | 4 | 4% | 5% | 3% | 0% | 6% | 6% | 0% | 0% | 0% | 13% | 0% | 0% | 0% | 0% |
| CBL1 mutation | 2 | 1 | 0% | 3% | 0% | 0% | 0% | 3%* | 0% | 0% | 0% | 0% | 0% | 0% | 0% | 0% |
| Copy number alteration/mutation . | Total number of cases . | Overall frequency, %† . | Frequency of copy number alterations and mutations by chromosomal abnormality and cytogenetic risk group . | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cytogenetic risk group . | Chromosomal abnormality . | |||||||||||||||
| Good . | Intermediate . | High . | ETV6-RUNX1 . | High Hyperdiploid . | B‐other . | t(1;19) . | IGH translocation . | KMT2A translocation . | iAMP21 . | Haploid . | Low hypodiploid‡ . | t(17;19) . | t(9;22) . | |||
| Total number of cases tested§ | 238 | 100 | 107 | 80 | 27 | 45 | 66 | 74 | 4 | 7 | 12 | 10 | 4 | 3 | 3 | 2 |
| CDKN2A/B deletion | 90 | 41 | 36%* | 54%* | 30%* | 34% | 37% | 59%** | 25% | 14% | 10%* | 20% | — | 100% | 33% | 100% |
| IKZF1 deletion | 52 | 23 | 11%** | 40%** | 26% | 2%** | 17% | 42%** | 25% | 29% | 20% | 40% | — | 50% | 0% | 0% |
| PAX5 alteration | 44 | 20 | 14% | 28% | 19% | 18% | 11%* | 32%** | 0% | 0% | 20% | 20% | — | 50% | 0% | 0% |
| ETV6 deletion | 36 | 16 | 18% | 11% | 26% | 34%** | 6%* | 10% | 50% | 0% | 0% | 60%** | — | 0% | 0% | 50% |
| TP53 alteration¶ | 29 | 10 | 7% | 7% | 28%** | 5% | 8% | 7% | 17% | 13% | 12% | 27% | 100%** | 40% | 0% | 0% |
| KRAS mutation | 26 | 12 | 11% | 14% | 10% | 0%** | 18% | 14% | 0% | 17% | 18% | 0% | 0% | 0% | 33% | 0% |
| NRAS mutation | 26 | 12 | 15% | 9% | 13% | 3%* | 23%** | 7% | 25% | 17% | 9% | 25% | 25% | 0% | 0% | 0% |
| P2RY8‐CRLF2 | 21 | 10 | 8% | 14% | 7% | 14% | 3%* | 12% | 25% | 29% | 10% | 10% | — | 0% | 0% | 0% |
| NR3C1 deletion | 18 | 9 | 9% | 6% | 22% | 14% | 6% | 7% | 0% | 0% | 18% | 11% | — | 50% | 67%** | 0% |
| PTPN11 mutation | 17 | 8 | 11% | 5% | 0% | 0% | 18%** | 6% | 0% | 0% | 0% | 0% | 0% | 0% | 0% | 0% |
| BTG1 deletion | 11 | 5 | 4% | 6% | 7% | 9% | 0%* | 6% | 0% | 14% | 0% | 0% | — | 50% | 33% | 0% |
| RB1 deletion | 11 | 5 | 3% | 10% | 0% | 2% | 3% | 12%** | 0% | 0% | 0% | 0% | — | 0% | 0% | 0% |
| EBF1 deletion | 10 | 5 | 4% | 6% | 0% | 7% | 2% | 6% | 0% | 14% | 0% | 0% | — | 0% | 0% | 0% |
| FLT3 mutation | 9 | 4 | 4% | 5% | 3% | 0% | 6% | 6% | 0% | 0% | 0% | 13% | 0% | 0% | 0% | 0% |
| CBL1 mutation | 2 | 1 | 0% | 3% | 0% | 0% | 0% | 3%* | 0% | 0% | 0% | 0% | 0% | 0% | 0% | 0% |
P values from χ2 tests: *P < .05; **P < .01.
Not all patients were successfully tested for all abnormalities.
Among a total of 5 low hypodiploid patients, 3 were tested for CNA and/or mutations, but all 5 were assessed for TP53 alterations (see ¶ footnote).
Only patients with a marrow relapse and with >20% blasts in the marrow at relapse were eligible for MLPA and mutation testing.
Among BCP‐ALL with a marrow relapse, 243 patients had successful cytogenetics, whereas 210 patients were successfully screened for mutations. The frequency of sequence mutations and deletions is <10%, so we used a denominator of comprising cases successfully tested for at least one of the abnormalities (n = 290).