Table 1.
Main cytogenetic subgroups in pediatric AML.
| Cytogenetic Subgroups |
Fusion Gene or Genes Involved |
Frequency in Childhood AML | Median Age (Y) (Range) | Special Features (Age, FAB, Phenotype, Treatment) | Secondary CA | Secondary Molecular Abnormalities | Risk Category |
References |
|---|---|---|---|---|---|---|---|---|
| BALANCED CA | ||||||||
| APL | ||||||||
| t(15;17)(q24;q21) | PML-RARA | 6–10% | 12 (1–18) |
M3 and M3v, Emergency (DIVC), Specific APL treatment (ATRA, ATO) |
tri 8, del(9q), ider(17)(q10) |
FLT3-ITD | Favorable | [20,39] |
| CBF leukemias | 20–25% | |||||||
| t(8;21)(q22;q22) | RUNX1-RUNX1T1 | 12–15% | 8 | M2, blasts with single and thin Auer rods, dysgranulopoiesis, CD19+, CD56+ | loss of X or Y, del(9q), tri 8, del(7q), tri 4 |
KIT, RAS, FLT3-ITD, FLT3-TKD, ASXL1/2, RAD21 | Favorable | [1,40,41,42,43] |
| inv(16)(p13q22)/ t(16;16)(p13;q22) |
CBFB-MYH11 | 5–9% | 9 | M4eo | tri 22, del(7q), tri 8 | KIT, RAS, FLT3-TKD, FLT3-ITD | Favorable | [1,40,41,42,43] |
| 11q23/KMT2Ar | KMT2A with multiple partners | 16–21% | 2.2 (0–18) |
M4 and M5, infants | tri 8 | High EVI1 expression, few mutations | Adverse or Intermediate | [44,45,46] |
| t(9;11)(p22;q23) | KMT2A-AF9(MLLT3) | 6–9% | 2.6 | Intermediate | [44,45,46] | |||
| t(11;19)(q23;p13.1) | KMT2A-ELL | 1–2% | 4.6 | Intermediate | [44,45,46] | |||
| t(11;19)(q23;p13.3) | KMT2A-ENL(MLLT1) | 1% | 7.1 | Intermediate | [44,45,46] | |||
| t(10;11)(p12;q23)/ ins(10;11)(p12;q23q13) * |
KMT2A-AF10(MLLT10) * | 2–3% | 1.3 | Adverse | [44,45,46] | |||
| t(6;11)(q27;q23) | KMT2A-AF6(MLLT4) | 1–2% | 12.4 | Adverse | [44,45,46] | |||
| 11p15/NUP98r |
NUP98 with multiple partners |
3–5% | 11 (1.3–18) |
Adverse | [36,47,48] | |||
| t(5;11)(q35;p15) ** | NUP98-NSD1 | 3–4% | 10.4 (1.2–19.4) |
M4,M5 71–77% of NUP98r 10–16% of NK |
tri 8, del(5q), CK | FLT3-ITD, WT1mut | Adverse | [36,46,47,49,50,51] |
| t(11;12)(p15;p13) ** | NUP98-KMD5A | 1–2% | 3.2 (0.01–18.5) |
10–30% of NUP98r 34% M7, 10% of M7 |
CK (numerous numerical and structural CA) | Low frequency of mutations | Adverse | [47,48,52] |
| 12p13 abnormalities |
NUP98-KMD5A del(12p) ETV6 (12p13.1) |
4% | Adverse | [22,28] | ||||
| t(7;12)(q36;p13) ** | ETV6; MNX1 | 1% | 0.5 y (0.2–2.3) |
Only infants (4% of infants) |
tri 19 | unknown | Adverse | [53] |
| Rare other balanced CA |
||||||||
| t(10;11)(p12;q14) | PICALM-MLLT10 | <1% | older children | Extramedullary disease, granulocytic sarcoma, CD7+ | tri 4, tri 19 | Intermediate | [46,50,54] | |
| inv(3)(q21q26.2)/ t(3;3)(q21;q26.2) |
GATA2; EVI1(MECOM) | 2% | 3 (2–18) |
Dysmyelopoiesis and platelet abnormalities | mon 7 | Adverse | [1,22,24] | |
| t(3;5)(q25;q35) | NPM1-MLF1 | <0.5% | 3.5 (2–13) |
M2, M4, M6, dysplasia | rare | unknown | Intermediate | [46,50,55] |
| t(6;9)(p22;q34) | DEK-NUP214 | 1–2% | 12 (2.6–20.4) |
M2/M4, dysplasia, basophilia. No infant cases |
loss of Y, tri 8, tri 13 | FLT3-ITD | Adverse | [56,57] |
| t(8;16)(p11;p13) | KAT6A-CREBBP | <1% | 1.2 (0–16) |
Peak in infants, spontaneous remission in a subset of neonates, DIVC, M4–M5, erythrophagocytosis | tri 1q, del(5q), del(7q), del(9q) | High HOXA9/HOXA10 expression |
Intermediate | [50,58] |
| t(16;21)(p11;q22) | FUS-ERG | 0.4% | 8.5 (2.0–17.5) |
no | tri 8, tri 10 |
Adverse | [50,59] | |
| t(16;21)(q24;q22) | RUNX1-CBFA2T3 | 0.2% | 6.8 (1.0–17) |
M1/M2, t-AML | tri 8, loss of Y | Gene expression profile close to RUNX1/RUNX1T1 | Favorable? | [50,59] |
| t(1;22)(p13;q13) | RBM15-MKL1 | 0.3% | 0.7 (0.1–2.7) |
Only M7 (5–10% of M7) Hepatosplenomegaly, fibrosis |
Mainly no ACA, HD karyotypes | Intermediate | [48,60,61,62,63,64] | |
| inv(16)(p13q24) ** | CBFA2T3-GLIS2 | 2–3% | 1.5 (0.3–17.2) |
Infants, 20% of non-DS-AMKL, extramedullary disease, CD56++ | Low HD karyotypes, tri 3, tri 21 | Few mutations | Adverse | [46,48,50,64,65,66,67] |
| t(9;22)(q34;q11) | BCR-ABL1 | 0.6% | Exclude CML-BP or MPAL mBCR Sensitivity to TKI |
Association with inv(16)/CBFB-MYH11 | Adverse | [1,14,22] | ||
| UNBALANCED CA | ||||||||
| Monosomy 5, del(5q) | / | 1.2% | 12.5 (0.3–20.7) |
M0 | del(17p), CK | Adverse | [7,22,28,68] | |
| Monosomy 7 *** | / | 3% | 7.2 (0–18) |
Exclude a primary CA and a predisposition syndrome (GATA2) | / | Adverse | [22,28,69] | |
| del(7q) *** | / | 3% | 7.6 (0–18) |
Exclude a primary abnormality and a predisposition syndrome | / | intermediate | [22,28,69] | |
| Trisomy 8 *** | / | 10–14% | 10.1 (0–18) |
Mainly a secondary abnormality Search for a primary CA | / | FLT3-ITD | Discussed | [70] |
| Hyperdiploidy (48~49–65 chr.) |
tri 8, tri 21, tri 19, tri 6, …. | 11% | 2 (0–17) |
AMKL, infants, Search for a primary CA | / | / | No significance | [56,71] |
| Complex karyotype ƒ |
/ | 8–17% | 3 (0–18) |
Exclude a primary CA |
/ | / | Discussed | [5,6,22,28] |
| Monosomal karyotype ƒƒ |
/ | 3–5% | 3.6 (0–17) |
Exclude a CBF leukemia |
/ | / | Discussed/ Adverse even after exclusion of mon 7 |
[5,6] |
| Normal Karyotype |
||||||||
| Normal karyotype |
/ | 20–26% | 8.8 (0–18) |
Search for a cryptic CA |
Search for prognostic mutations: FLT3-ITD, CEBPAdm, NPM1 |
According to cryptic CA or to mutations | [7,22,28,36,46] |
NOTE 1. Risk categories were defined according to Harrison [22] and Von Neuhoff 2010 [28]: Favorable, Intermediate and Adverse correspond to 5-year survival >70%, 50–70% and <50%, respectively. NOTE 2. Infants: children under 2 years. Abbreviations: APL: acute promyelocytic leukemia; CA: cytogenetic abnormality; CK: complex karyotype (at least 3 CAs); CML-BP: chronic myeloid leukemia blast phase; DIVC: disseminated intravascular coagulation; HD: hyperdiploid karyotype; mBCR: minor BCR; MPAL: mixed phenotype acute leukemia, mon: monosomy; r: rearrangement; TKI: tyrosine kinase inhibitors; tri: trisomy. * A complex rearrangement or a cryptic insertion is necessary to create a KMT2A-MLLT10 fusion gene (see text); thus, FISH with a KMT2A probe is mandatory. ** Cryptic abnormality requiring molecular methods for detection: FISH and/or PCR-based method. *** As a primary abnormality. ƒ At least 3 independent CAs in the absence of a WHO-designated recurring translocation or inversion. Some authors include in the definition “with at least one structural abnormality” [5,28]. ƒƒ Loss of at least two autosomes or loss of one autosome and the presence of a structural abnormality (excluding mar or ring), excluding CBF AML.