Selected genetic abnormalities most often found in pediatric AML [10]
| Genetic aberration | Occurrence frequency | Effect | Prognostic significance |
|---|---|---|---|
| t(8;21)(q22;q22) RUNX1–RUNX1T1 | 10–12% | Impaired differentiation, effect on cell proliferation and survival | Favourable |
| inv(16) or t(16;16)(p13;q22) CBFB–MYH11 | 5–6% | Impaired differentiation, effect on cell proliferation | Favorable |
| KMT2A (MLL) rearrangements | 10–15% | Altered HOX gene expression pattern, abnormal differentiation | The presence of t(9;11) (p21; q23) contributes to favorable prognosis; in other cases unfavorable |
| t(15;17) (q22;q21) PML–RARA | 5–9% | Differentiation impaired | Favourable |
| Monosomy 7 | 5% | Suppressor gene function loss | Unfavorable |
| Intra-tandem FLT3 duplication | 10–15% | Increased proliferation | Unfavorable |
Hyperdiploidy characteristics in ALL [36]
| MN | Characteristics | Prognosis | |
|---|---|---|---|
| Tetraploidy near hyperdiploidy (NT) | 82–94 | L2; T-ALL immunophenotype; older age on the day of diagnosis; CD13, CD15, and CD33 expression | Unfavorable |
| Tetraploidy near hyperdiploidy | 66–73 | pre-B-ALL immunophenotypy | Favorable |
| High hyperdiploidy (HH) | 51–68 | L1 or L2; presence of additional chromosome u X, 4, 6, 10, 14, 17, 18, or 21; low WBC and LDH; the age between 5 and 10; CD123, CD10, CD66c overexpression, no CD45 expression | Favorable |
| Low hyperdiploidy | 47–50 | Presence of additional chromosome 21, 8, 10, or X | Intermediate |
Characteristics of numerical aberrations in AML [36]
| MN | Characteristics | Prognosis | |
|---|---|---|---|
| Tetraploidy | 81–103 | association with additional chromosomes 21, 19, and 8 | No data available |
| Hyperdiploidy | 48–65 | median age 2 years; women; FAB M7; relationship with the presence of extra chromosomes: 8 (41%), 21 (19%), 19 (18%), and 6 (14%); CD4, TdT, CD19, and CD7 expression | No data available |
| Hypodiploidy | 42–45 | older age; men; FAB M2; presence of t(8;21) (q22;q22) | No data available |
Hypodiploidy characteristics in ALL [36]
| MN | Characteristics | Prognosis | |
|---|---|---|---|
| High hypodiploidy | 42–45 | complex karyotype containing chromosomes 7, 9, 12; T-ALL or common / pre-B-ALL immunophenotype | Unfavorable |
| Low hypodiploidy | 33–39 | monosomy of chromosome 3, 7, 15, 16, 17; common / pre-B-ALL immunophenotype; | Unfavorable |
| Haploidy near hypodiploidy | 23–29 | monosomy of chromosome 3, 7, 15, 16, 17; common / pre-B-ALL immunophenotype; | Unfavorable |
Immunological classification of acute lymphoblastic leukemia based on B-lymphocyte precursor cells according to EGIL
| cytCD79, CD19, CD22 | CD10 | cytIgM | kappa/lambda | |
|---|---|---|---|---|
| Pro-B-ALL (B-I) | + | − | − | − |
| Common-B-ALL (B-II) | + | + | − | − |
| Pre-B-ALL (B-III) | + | +/− | + | − |
| Mature-B-ALL (B-IV) | + | +/− | +/− | + |
Selected genetic abnormalities most frequently found in pediatric BCP-ALL [10, 26]
| Genetic aberration | Occurrence frequency | Effect | Prognostic significance |
|---|---|---|---|
| t(9;22)(q34;q11.1)-BCR-ABL1 | 2–3% | Mitogenic signalling activation, apoptosis suppression, altered cell adhesion | Unfavorable |
| t(12;21)(p13;q22)-ETV6-RUNX1 | 20–25% | HOX genes impaired expression in lymphopoiesis | Favorable |
| t(1;19)(q23;p13.3)-TCF3-PBX1 | 5–6% | Differentiation disorder | Favorable in intensified treatment; not relevant in AIEOP-BFM 2017 |
| KMT2A (MLL) rearangements | 5–8% (infants appr 70%, children > 1 year old, appr 2%) | Effect on HOX gene expression | Unfavorable in infants; unfavorable in the presence of t(4;11)(q21;q23) regardless of age |
| Chromosome hyperdiploidy > 51 | 20–30% | Mechanism poorly recognized | Favorable (especially in the presence of trisomy 4, 10 i 17); not relevant in AIEOP-BFM 2017 |
| Chromosome hyperdiploidy ≤ 44 | 5–6% | Mechanism poorly recognized | Unfavorable |
| CDKN2A deletion | 2–30% | Proliferation control loss | Not relevant |
WHO immunological classification of acute myeloid leukemia [20]
| Acute myeloid leukemias with repeated genetic changes |
| AML with t(8;21)(q22;q22.1); RUNX1-RUNX1T |
| AML with inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); CBFB-MYH11 |
| APL with t(15;17)(q24.1;q21.2); PML-RARA |
| AML with t(9;11)(p21.3;q23.3); KMT2A-MLLT3 |
| AML with t(6;9)(p23;q34.1); DEK-NUP214 |
| AML with inv(3)(q21.3;q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM |
| AML with t(1;22)(p13.3;q13.1); RBM15-MKL1 |
| AML with t(9;22)(q34.1;q11.2); BCR-ABL1 |
| AML with NPM1 mutation |
| AML with CEBPA mutation |
| AML with RUNX1 mutation |
| Acute myeloid leukemias with myelodysplasia |
| Treatment-induced acute myeloid leukemias and myelodysplastic syndromes |
| Acute myeloid leukemias, not classified anywhere |
| Acute myeloid leukemia minimally differentiated |
| Acute myeloid leukemia without maturation |
| Acute myeloid leukemia with maturation |
| Acute myelomonocytic leukemia |
| Acute monoblastic and monocytic leukemia |
| Acute erythroblastic leukemia |
| Acute megakaryoblastic leukemia |
| Acute basophilic leukemia |
| Acute panmyelosis with fibrosis |
| Myelosarcoma |
| AML associated with Down syndrome |
Immunological classification of acute lymphoblastic leukemia based on T-lymphocyte precursor cells according to EGIL
| cytCD3, CD7 | CD2, CD5, CD4 and/or CD8 | CD1a | CD3 | |
|---|---|---|---|---|
| Pro-T-ALL (T-I) | + | − | − | − |
| Pre-T-ALL (T-II) | + | + | − | − |
| Cortical-T-ALL (T-III) | + | +/− | + | − |
| Mature-T-ALL (T-IV) | + | +/− | − | + |
WHO immunological classification of acute lymphoblastic leukemia [20]
| Leukemia / B-cell lymphoblastic lymphoma, unspecified |
| B-cell leukemia / lymphoblastic lymphoma with reproducible genetic changes |
| Acute leukemia / B-lymphoma with t(9;22)(q34.1;q11.2); BCR-ABL1 |
| Acute leukemia / B lymphoblastic lymphoma with t(v;11q23.3); with KMT2A (MLL) rearrangements |
| Acute leukemia / B-lymphoma with t(12;21)(p13.2;q22.1); ETV6-RUNX1 |
| Acute leukemia / B lymphoblastic lymphoma with hyperdiploidy |
| Acute leukemia / B-lymphoblastic lymphoma with hypodiploidy |
| Acute leukemia / B-lymphoma with t(5;14)(q31.1; q32.3); IL3-IGH |
| Acute leukemia / B-lymphoma with t(1;19) (q23;1332); TCF3-PBX1 |
| Acute leukemia / B lymphoblastic lymphoma, similar to BCR-ABL1 + |
| Acute leukemia / B-lymphoblastic lymphoma with intra-chromosomal disease chromosome 21 amplification |
| Acute leukemia / T-lymphoblastic lymphoma |
| Acute leukemia / lymphoblastic lymphoma from early T-cell precursors |
| Acute leukemia / NK lineage lymphoblastic lymphoma |
Selected genetic abnormalities most often found in pediatric T-ALL [10, 26]
| Genetic aberration | Occurrence frequency | Effect | Prognostic significance |
|---|---|---|---|
| Translocations of oncogenes responsible for TCR (TLX1, TLX3, TAL1, LMO1, LMO2, HOXA) expression | 40–50% | Protein overexpression, impaired differentiation | t(10;14) with TLX1 overexpression associated with favorable prognosis; TLX3 overexpression with unfavorable prognosis |
| del(1)(p32) with SIL–TAL1 fusion | 20–30% | TAL1 overexpression, impaired differentiation | Not relevant |
| CDKN2A deletion | 60–70% | Loss of proliferation control | Not relevant |
| KMT2A (MLL) rearangement | 5–10% | Effect on HOX gene expression | Not relevant |
| NOTCH1 mutation | 40–50% | Self-renewal capacity increase | Favorable in some therapeutic protocols |