Table 1.
Genetic alterations and potential targeted therapy in pediatric B- and T-acute lymphoblastic leukemia.
| Classification | Frequency | Prognosis | Potential Therapeutic Implications |
|---|---|---|---|
| B-cell acute lymphoblastic leukemia | |||
| High hyperdiploidy (HeH) | ~25% of pediatric ALL | Excellent prognosis | Reduction of intensity |
| Hypodiploidy | ~1–2% of ALL | Inferior survival | BCL2 inhibitors |
| t(12;21)(p13;q22) encoding ETV6-RUNX1 | ~25% of standard risk pediatric B-ALL | Excellent prognosis | Reduction of intensity |
| ETV6-RUNX1-like | Favorable prognosis | Reduction of intensity | |
| KMT2A (MLL) rearranged | ~75% of infants with B-ALL | Dismal survival | DOT1L inhibitors, menin inhibitors, proteasome inhibitors, HDAC inhibitors, BCL2 inhibitors |
| t(9;22)(q34;q11.2) encoding BCR-ABL1 | 3–5% of pediatric B-ALL | Historically poor prognosis, improved with tyrosine kinase inhibitors | ABL1 inhibitors, FAK inhibitors, rexinoids, BCL2 inhibitors |
| t(1;19)(q23;p13.3) encoding TCF3-PBX1 | 4% of ALL | Favorable prognosis | |
| iAMP21 | ~2% of pediatric B-ALL, older children | High-risk therapy for good outcomes | Intensification of therapy |
| Ph-like | 12–15% of pediatric B-ALL | Poor survival | ABL1 inhibitors, JAK inhibitors, PI3K inhibitors, BCL2 inhibitors |
| DUX4 rearranged | 7% of childhood B-ALL | Favorable prognosis | Reduction of intensity |
| MEF2D rearranged | 3–6% of childhood B-ALL | Poor survival | HDAC inhibitors |
| ZN384 rearranged | 3% of childhood B-ALL | Intermediate prognosis | FLT3 inhibitors |
| NUTM1 rearranged | 1–2% of pediatric B-ALL | Excellent prognosis | HDAC inhibitors, bromodomain inhibitors |
| T-cell acute lymphoblastic leukemia | |||
| NOTCH1 mutation | >50% of childhood T-ALL | Favorable outcomes | Standard chemotherapy |
| TAL1 deregulation | 30% of childhood T-ALL | Enrichment of mutations in PI3K signaling pathway | PI3K inhibitors, nelarabine, BCL2 inhibitors |
| TLX3 deregulation | 19% of childhood T-ALL | Poor prognosis | Nelarabine, BCL2 inhibitors |
| HOXA deregulation | 5% of childhood T-ALL | Frequent mutations in JAK-STAT pathway, KMT2A rearrangements | JAK inhibitors, nelarabine, BCL2 inhibitors |
| TLX1 deregulation | 8% of T-ALL | Favorable prognosis | Nelarabine, BCL2 inhibitors |
| LMO2/LYL1 deregulation | 13% of childhood T-ALL | Poor prognosis | JAK inhibitors, nelarabine, BCL2 inhibitors |
| NUP214-ABL1 with 9q34 amplification | ~5–10% of childhood T-ALL | Neutral prognosis | ABL1 inhibitors, nelarabine, BCL2 inhibitors |
| NKX2-1 deregulation | 8% of T-ALL | Frequent co-operating mutation in ribosomal genes | Nelarabine, BCL2 inhibitors |
| Early T-cell precursor ALL | 10–15% of T-ALL | Poor prognosis | JAK inhibitors, BCL2 inhibitors |