Definition and risk stratification of B-ALL subgroups using RNA-seq
| Subtype . | No. (N = 377) . | % . | Method . | Criteria . | 5-y CIR (%) . | 95% CI . | 5-y OS (%) . | 95% CI . | RNA-seq risk stratification . |
|---|---|---|---|---|---|---|---|---|---|
| High hyperdiploid | 89 | 24 | a | No. of chromosomes >50 | 5.5 | 1.7-12.6 | 98.8 | 91.8-99.8 | Low |
| Hypodiploid | 2 | 1 | a | No. of chromosomes 31-44 | 50.0 | 0.0-96.0 | 50.0 | 0.6-91.0 | High |
| Near haploid | 3 | 1 | a | No. of chromosomes 24-30 | 50.0 | 0.0-96.0 | 50.0 | 0.6-91.0 | High |
| ETV6-RUNX1 | 74 | 20 | b | ETV6-RUNX1 rearrangement | 5.2 | 1.3-13.1 | 100.0 | 100.0 | Low |
| ETV6-RUNX1-like | 9 | 2 | c | Coclustered with ETV6-RUNX1 rearrangement | 12.7 | 0.5-45.3 | 88.9 | 43.3-98.4 | Intermediate |
| DUX4 | 51 | 14 | c | In the cluster containing all DUX4-IGH rearrangements | 8.9 | 2.8-19.5 | 97.8 | 85.3-99.7 | Low |
| PBX1 | 19 | 5 | b | PBX1 rearrangement | 5.6 | 0.3-23.1 | 94.4 | 66.6-99.2 | Intermediate |
| ZNF384 | 17 | 5 | b | ZNF384 rearrangement | 6.3 | 0.4-25.5 | 93.3 | 61.3-99.0 | Low (EP300) Intermediate (other partners) |
| ZNF384-like | 2 | 1 | c | Coclustered with ZNF384 rearrangement | NA | NA | Intermediate | ||
| BCR-ABL1 | 9 | 2 | b | BCR-ABL1 rearrangement | 37.5 | 7.2-69.4 | 75.0 | 31.5-93.1 | High |
| BCR-ABL1-like | 8 | 2 | c+b | Coclustered with BCR-ABL1, no CRLF2 rearrangement | 37.5 | 6.9-69.8 | 75.0 | 31.5-93.1 | High |
| CRLF2 | 10 | 3 | b | CRLF2 rearrangement | 20.0 | 2.6-49.2 | 59.1 | 16.0-86.0 | High |
| MEF2D | 4 | 1 | b | MEF2D rearrangement | 0.0 | 0.0 | 100.0 | 100.0 | High |
| KMT2A | 11 | 3 | b | KMT2A rearrangement | 54.3 | 16.7-81.2 | 64.8 | 25.3-87.2 | High |
| NUTM1 | 3 | 1 | b | NUTM1 rearrangement | 0.0 | 0.0 | 100.0 | 100.0 | Intermediate |
| PAX5alt | 36 | 10 | c+a+b+d | In the cluster enriched with PAX5 alterations; no other subtype-defining events | 18.1 | 6.3-34.7 | 89.2 | 69.7-96.5 | Intermediate |
| PAX5 P80R | 2 | 1 | d+c | PAX5 P80R mutation, clustered separately | NA | NA | Intermediate | ||
| TCF3-HLF | 1 | 0.3 | b | TCF3-HLF rearrangement | NA | NA | High | ||
| IGH-CEBPE | 1 | 0.3 | b | IGH-CEBPE rearrangement | 0.0 | 0.0 | 100.0 | 100.0 | Intermediate |
| Others | 26 | 7 | a+b+c+d | Other patients | 20.7 | 7.3-39.0 | 94.1 | 65.0-99.1 | Intermediate |
| Subtype . | No. (N = 377) . | % . | Method . | Criteria . | 5-y CIR (%) . | 95% CI . | 5-y OS (%) . | 95% CI . | RNA-seq risk stratification . |
|---|---|---|---|---|---|---|---|---|---|
| High hyperdiploid | 89 | 24 | a | No. of chromosomes >50 | 5.5 | 1.7-12.6 | 98.8 | 91.8-99.8 | Low |
| Hypodiploid | 2 | 1 | a | No. of chromosomes 31-44 | 50.0 | 0.0-96.0 | 50.0 | 0.6-91.0 | High |
| Near haploid | 3 | 1 | a | No. of chromosomes 24-30 | 50.0 | 0.0-96.0 | 50.0 | 0.6-91.0 | High |
| ETV6-RUNX1 | 74 | 20 | b | ETV6-RUNX1 rearrangement | 5.2 | 1.3-13.1 | 100.0 | 100.0 | Low |
| ETV6-RUNX1-like | 9 | 2 | c | Coclustered with ETV6-RUNX1 rearrangement | 12.7 | 0.5-45.3 | 88.9 | 43.3-98.4 | Intermediate |
| DUX4 | 51 | 14 | c | In the cluster containing all DUX4-IGH rearrangements | 8.9 | 2.8-19.5 | 97.8 | 85.3-99.7 | Low |
| PBX1 | 19 | 5 | b | PBX1 rearrangement | 5.6 | 0.3-23.1 | 94.4 | 66.6-99.2 | Intermediate |
| ZNF384 | 17 | 5 | b | ZNF384 rearrangement | 6.3 | 0.4-25.5 | 93.3 | 61.3-99.0 | Low (EP300) Intermediate (other partners) |
| ZNF384-like | 2 | 1 | c | Coclustered with ZNF384 rearrangement | NA | NA | Intermediate | ||
| BCR-ABL1 | 9 | 2 | b | BCR-ABL1 rearrangement | 37.5 | 7.2-69.4 | 75.0 | 31.5-93.1 | High |
| BCR-ABL1-like | 8 | 2 | c+b | Coclustered with BCR-ABL1, no CRLF2 rearrangement | 37.5 | 6.9-69.8 | 75.0 | 31.5-93.1 | High |
| CRLF2 | 10 | 3 | b | CRLF2 rearrangement | 20.0 | 2.6-49.2 | 59.1 | 16.0-86.0 | High |
| MEF2D | 4 | 1 | b | MEF2D rearrangement | 0.0 | 0.0 | 100.0 | 100.0 | High |
| KMT2A | 11 | 3 | b | KMT2A rearrangement | 54.3 | 16.7-81.2 | 64.8 | 25.3-87.2 | High |
| NUTM1 | 3 | 1 | b | NUTM1 rearrangement | 0.0 | 0.0 | 100.0 | 100.0 | Intermediate |
| PAX5alt | 36 | 10 | c+a+b+d | In the cluster enriched with PAX5 alterations; no other subtype-defining events | 18.1 | 6.3-34.7 | 89.2 | 69.7-96.5 | Intermediate |
| PAX5 P80R | 2 | 1 | d+c | PAX5 P80R mutation, clustered separately | NA | NA | Intermediate | ||
| TCF3-HLF | 1 | 0.3 | b | TCF3-HLF rearrangement | NA | NA | High | ||
| IGH-CEBPE | 1 | 0.3 | b | IGH-CEBPE rearrangement | 0.0 | 0.0 | 100.0 | 100.0 | Intermediate |
| Others | 26 | 7 | a+b+c+d | Other patients | 20.7 | 7.3-39.0 | 94.1 | 65.0-99.1 | Intermediate |
The methods used to define each subgroup can be categorized into 4 types: (a) digital karyotyping, (b) identification of oncogene rearrangement, (c) gene expression profiling, and (d) variant calling. Patients whose disease had multiple features were classified according to gene expression clustering.