Genetic alterations of diagnostic use and/or therapeutic or prognostic value in routine clinical practice in ALL
| Disease subtype* . | Genes† . | Frequency, % . | Normal function . | Technology used to detect . | Prognostic marker‡ . | Genotype-directed therapies . |
|---|---|---|---|---|---|---|
| B-ALL | BCR-ABL1 | 25 | Tyrosine kinase | FISH, PCR | Adverse | TKIs |
| BCR-ABL1-like | 10-20 | Various but nearly all are mitogenic-signaling molecules | GEP | Adverse | TKIs | |
| iAmp 21 | 2 | RUNX1 transcription factor | FISH | Adverse | ||
| Hypodiploidy (≤45 chromosomes) | 3-6 | Karyotype | Adverse | |||
| t(17;19)(q22;p13); TCF3-HLF | Rare | Transcription factor | Karyotype, FISH | Adverse | ||
| t(v;11q23.3); KMT2A fusions | 2-10 | Histone methyltransferase | Karyotype, FISH | Adverse | ||
| High hyperdiploidy (51-65 chromosomes) | 20%-30% (children); 5%-10% (adults) | Karyotype | Favorable | |||
| t(12;21)(p13;q22); ETV6-RUNX1 | 20%-30% (children) | Transcription factor | Karyotype, FISH | Favorable | ||
| t(5;14)(q31.1;q32.3); IL3-IGH | Rare | Cytokine signaling | Karyotype, FISH | |||
| t(1;19)(q23;p13.3); TCF3-PBX1 (E2A-PBX1) | 2-6 | Transcription factor | Karyotype, FISH | |||
| T-ALL | NOTCH1 | 50-60 | Signaling molecule regulating T-cell development | Sequencing | Clinical trials of anti-NOTCH therapies | |
| CDKN2A/B | 50-60 | Cell cycle regulation | Karyotype, FISH | |||
| PHF6 | 20-40 | Unknown | Sequencing | |||
| FBXW7 | 10-15 | E3 Ubiquitin ligase for NOTCH1 | Sequencing | |||
| ETP-ALL | RUNX1 | 20 | Transcription factor | Sequencing | Adverse | |
| DNMT3a | 15 | DNA methyltransferase | Sequencing | Adverse | ||
| ETV6 | 10-15 | Transcription factor | Sequencing | |||
| IDH1/2 | α-KG hydroxylase in TCA cycle | Sequencing | Trials involving mutant IDH1/2 inhibitors | |||
| FLT3 | 5-10 | Tyrosine kinase | Sequencing | Trials involving FLT3 inhibitors | ||
| TET2 | DNA hydroxymethylation | Sequencing |
| Disease subtype* . | Genes† . | Frequency, % . | Normal function . | Technology used to detect . | Prognostic marker‡ . | Genotype-directed therapies . |
|---|---|---|---|---|---|---|
| B-ALL | BCR-ABL1 | 25 | Tyrosine kinase | FISH, PCR | Adverse | TKIs |
| BCR-ABL1-like | 10-20 | Various but nearly all are mitogenic-signaling molecules | GEP | Adverse | TKIs | |
| iAmp 21 | 2 | RUNX1 transcription factor | FISH | Adverse | ||
| Hypodiploidy (≤45 chromosomes) | 3-6 | Karyotype | Adverse | |||
| t(17;19)(q22;p13); TCF3-HLF | Rare | Transcription factor | Karyotype, FISH | Adverse | ||
| t(v;11q23.3); KMT2A fusions | 2-10 | Histone methyltransferase | Karyotype, FISH | Adverse | ||
| High hyperdiploidy (51-65 chromosomes) | 20%-30% (children); 5%-10% (adults) | Karyotype | Favorable | |||
| t(12;21)(p13;q22); ETV6-RUNX1 | 20%-30% (children) | Transcription factor | Karyotype, FISH | Favorable | ||
| t(5;14)(q31.1;q32.3); IL3-IGH | Rare | Cytokine signaling | Karyotype, FISH | |||
| t(1;19)(q23;p13.3); TCF3-PBX1 (E2A-PBX1) | 2-6 | Transcription factor | Karyotype, FISH | |||
| T-ALL | NOTCH1 | 50-60 | Signaling molecule regulating T-cell development | Sequencing | Clinical trials of anti-NOTCH therapies | |
| CDKN2A/B | 50-60 | Cell cycle regulation | Karyotype, FISH | |||
| PHF6 | 20-40 | Unknown | Sequencing | |||
| FBXW7 | 10-15 | E3 Ubiquitin ligase for NOTCH1 | Sequencing | |||
| ETP-ALL | RUNX1 | 20 | Transcription factor | Sequencing | Adverse | |
| DNMT3a | 15 | DNA methyltransferase | Sequencing | Adverse | ||
| ETV6 | 10-15 | Transcription factor | Sequencing | |||
| IDH1/2 | α-KG hydroxylase in TCA cycle | Sequencing | Trials involving mutant IDH1/2 inhibitors | |||
| FLT3 | 5-10 | Tyrosine kinase | Sequencing | Trials involving FLT3 inhibitors | ||
| TET2 | DNA hydroxymethylation | Sequencing |
B-ALL, B-cell acute lymphoblastic leukemia; ETP-ALL, early T-cell precursor acute lymphoblastic leukemia; GEP, gene expression profiling; T-ALL, T-cell acute lymphoblastic leukemia. Other abbreviations are explained in Table 1.
Additional recurrent mutations and structural variations are known to be present in B- and T-ALL but only those with known diagnostic, prognostic, and/or therapeutic utility are shown here.
Mutations in gene names in bold are of diagnostic value.
Those genes left blank do not have clear prognostic relevance currently.