Selected recurrent genetic alterations in childhood T-ALL
| Genetic lesion . | Incidence in pediatric T-ALL, % . | Outcome . | Potential therapeutic implications . | Comments . |
|---|---|---|---|---|
| Recurrent structural chromosomal aberrations | ||||
| t(1;14)(p32;q11); t(1;7)(p32)(q34);TAL1 fusions | 30-40 | Possibly unfavorable | Associated with PTEN/PI3K mutations and 6q deletion | |
| t(10;14)(q24;q11); TLX1 fusion | 5-10 | Possibly favorable | Given co-occurrence of lesions, resulting signaling pathway activation, possible utility of JAK inhibitors and MEK inhibitors | Associated with PHF6 mutations, JAK/STAT- and Ras-activated signaling mutations; NUP214-ABL1 fusions that activate STAT5 and Ras-MAPK pathways |
| t(11;14)(p15;q11), t(5;14)(q35;q32); TLX3 fusions | 20-25 | Possibly unfavorable | Given co-occurrence of lesions, resulting signaling pathway activation, possible utility of JAK inhibitors and MEK inhibitors | Associated with near–ETP-ALL; association with WT1 mutations, PHF6 mutations, JAK/STAT- and Ras-activated signaling mutations; NUP214-ABL1 fusions that activate STAT5 and Ras-MAPK pathways |
| t(11;14)(p15;q11); LMO1 fusion | <5 | Possibly unfavorable | Usually occurs with LYL1 or TAL1 fusions | |
| t(11;13)(p15;q11); LMO2 fusion | 3-5 | Possibly unfavorable | Usually occurs with LYL1 or TAL1 fusions; highly enriched for ETP-ALL | |
| 7p15 translocations; HOXA overexpression | 2-3 | Possibly unfavorable | Associated with PHF6 and EZH2 mutations | |
| 11q23 translocations; KMT2A rearrangements | 5 | Some studies possibly unfavorable, some possibly favorable | Included in HOXA-overexpressing subgroup | |
| t(10;11)(p13;q21); PICALM-MLLT10 | 5-10 | Possibly unfavorable | Included in HOXA-overexpressing subgroup; associated with EZH2 mutations | |
| Inv14(q11;q13); NKX2-1 fusion | ∼5 | Neutral | Associated with LEF1 deletion/mutation | |
| Common molecular lesions | ||||
| NOTCH1 mutations | >70 | Possibly favorable | γ secretase inhibitors | Associated with CDKN2A/B deletions and FBXW7 deletions/mutation; less common in TAL1 T-ALL |
| CDKN2A/B deletion | 50-60 | Possibly favorable | Associated with NOTCH1 mutations; less common in ETP-ALL | |
| FBXW7 mutations/deletions | ∼20 | Possibly favorable | Negative regulator of NOTCH1; mutations/deletions associated with NOTCH1 mutations | |
| PTEN mutations | ∼20 | Possibly unfavorable | Associated with TAL1 T-ALL | |
| PHF6 deletions/mutations | 20-25 | Epigenetic regulator; mutations/deletions common in TLX1/3, HOXA-overexpressing, TAL1, and NKX2-1 T-ALL | ||
| Ras pathway mutations | Possibly unfavorable | MEK and PI3K inhibitors | Associated with ETP-ALL |
| Genetic lesion . | Incidence in pediatric T-ALL, % . | Outcome . | Potential therapeutic implications . | Comments . |
|---|---|---|---|---|
| Recurrent structural chromosomal aberrations | ||||
| t(1;14)(p32;q11); t(1;7)(p32)(q34);TAL1 fusions | 30-40 | Possibly unfavorable | Associated with PTEN/PI3K mutations and 6q deletion | |
| t(10;14)(q24;q11); TLX1 fusion | 5-10 | Possibly favorable | Given co-occurrence of lesions, resulting signaling pathway activation, possible utility of JAK inhibitors and MEK inhibitors | Associated with PHF6 mutations, JAK/STAT- and Ras-activated signaling mutations; NUP214-ABL1 fusions that activate STAT5 and Ras-MAPK pathways |
| t(11;14)(p15;q11), t(5;14)(q35;q32); TLX3 fusions | 20-25 | Possibly unfavorable | Given co-occurrence of lesions, resulting signaling pathway activation, possible utility of JAK inhibitors and MEK inhibitors | Associated with near–ETP-ALL; association with WT1 mutations, PHF6 mutations, JAK/STAT- and Ras-activated signaling mutations; NUP214-ABL1 fusions that activate STAT5 and Ras-MAPK pathways |
| t(11;14)(p15;q11); LMO1 fusion | <5 | Possibly unfavorable | Usually occurs with LYL1 or TAL1 fusions | |
| t(11;13)(p15;q11); LMO2 fusion | 3-5 | Possibly unfavorable | Usually occurs with LYL1 or TAL1 fusions; highly enriched for ETP-ALL | |
| 7p15 translocations; HOXA overexpression | 2-3 | Possibly unfavorable | Associated with PHF6 and EZH2 mutations | |
| 11q23 translocations; KMT2A rearrangements | 5 | Some studies possibly unfavorable, some possibly favorable | Included in HOXA-overexpressing subgroup | |
| t(10;11)(p13;q21); PICALM-MLLT10 | 5-10 | Possibly unfavorable | Included in HOXA-overexpressing subgroup; associated with EZH2 mutations | |
| Inv14(q11;q13); NKX2-1 fusion | ∼5 | Neutral | Associated with LEF1 deletion/mutation | |
| Common molecular lesions | ||||
| NOTCH1 mutations | >70 | Possibly favorable | γ secretase inhibitors | Associated with CDKN2A/B deletions and FBXW7 deletions/mutation; less common in TAL1 T-ALL |
| CDKN2A/B deletion | 50-60 | Possibly favorable | Associated with NOTCH1 mutations; less common in ETP-ALL | |
| FBXW7 mutations/deletions | ∼20 | Possibly favorable | Negative regulator of NOTCH1; mutations/deletions associated with NOTCH1 mutations | |
| PTEN mutations | ∼20 | Possibly unfavorable | Associated with TAL1 T-ALL | |
| PHF6 deletions/mutations | 20-25 | Epigenetic regulator; mutations/deletions common in TLX1/3, HOXA-overexpressing, TAL1, and NKX2-1 T-ALL | ||
| Ras pathway mutations | Possibly unfavorable | MEK and PI3K inhibitors | Associated with ETP-ALL |
ETP-ALL, early thymic precursor or early T-cell precursor acute lymphoblastic leukemia.