Table 5.
Characteristics and Clinical Outcomes of Selected Subtypes of Childhood AML
| Subtype | Affected Genes | Gene Functions | Frequency (%) | Clinical Characteristics | 5-Year EFS (%) | 5-Year OS (%) |
|---|---|---|---|---|---|---|
| Rearrangements | ||||||
| t(8;21)(q22;q22) | ETO-AML1 | Transcription factors | 12 | Associated with chloromas | 55–71 | 75–85 |
| inv(16)(p13;q22) | MYH11-CBF | Muscle protein/transcription factor | 8 | Eosinophilia with dysplastic basophilic granules | 72–88 | 75–85 |
| t(8;16) | MOZ-CBP | Transcription factors | 1 | High WBCs, chloromas, etoposide-related secondary AML | ID*† | ID |
| t(15;17)(q22;q12) | PML-RAR | Transcription factors/retinoid receptor | 12 | Associated with FAB M3, Auer rods common; FAB M3; ATRA-sensitive | 71† | 90† |
| t(11;17)(q23;q12) | PLZF-RARA | Transcription factors/retinoid receptor | Rare | Associated with FAB M3, Auer rods common; FAB M3; ATRA-resistant | ID | ID |
| t(1;22) | RBM15-MKL1 | RNA binding protein, DNA binding protein | 2–3 | Associated with FAB M7 in Down syndrome and non–Down syndrome | ID | ID |
| t(6;9)(p23;q34) | DEK-NUP214(CAN) | Transcription factor/nuclear transport | Rare | Basophilia and multilineage dysplasia; associated with FLT3-ITD and TdT+ | ID | ID |
| MLL | MLL (partner genes) | Histone methyltransferase | 18 | |||
| t(1;11)(q21;q23) | AF1q (MLLT11) | Function unknown, causes short half-life | 3 | 76% < age 2 years; 20% and 48% FAB M4 and M5, respectively | 92 | 100 |
| t(4;11)(q21;q23) | AF4 (MLLT2) | Associated with EAP10 | 2 | 61% < age 2 years; 17% and 42% FAB M4 and M5, respectively | 29 | 27 |
| t(6;11)(q27;q23) | AF6 (MLLT4) | Functions as dimerization domain | 5 | 9% < age 2 years; 57% ≥ 10 years; 35% and 41% FAB M4 and M5, respectively | 11 | 22 |
| t(9;11)(p22;q23) | AF9 (MLLT3) | ENL homolog, associated with EAP | 43 | 42% < age 2 years; 81% is FAB M5 | 50 | 63 |
| t(10;11)(p11.2;q23) | AF10 (MLLT10) | Interacts with DOT1L | 2 | 75% < age 2 years; 27% and 55% FAB M4 and M5, respectively | 17 | 27 |
| t(10;11)(p12;q23) | AF10 (MLLT10) | Interacts with DOT1L | 13 | 62% < age 2 years; 72% is FAB M5 | 31 | 45 |
| t(11;19)(q23;p13) | ELL or ENL (MLLT1) | Binds histone H3, Assembles EAP | 4 | 58% < age 2 years; 42% and 45% FAB M4 and M5, respectively | 49 | 49 |
| t(11;19)(q23;p13.1) | ELL or ENL (MLLT1) | Binds histone H3, Assembles EAP | 4 | 41% < age 2 years; 30% and 33% FAB M4 and M5 respectively | 46 | 61 |
| t(11;19)(q23;p13.3) | ELL or ENL (MLLT1) | Binds histone H3, Assembles EAP | 3 | 36% < age 2 years; 44% ≥ age 10 years; 20% and 40% FAB M4 and M5 | 46 | 47 |
| t(11;17)(q23;q21) | AF17 (MLLT6), LASP1 | F-actin rick cytoskeletal activity | 2 | 33% < age 2 years; 42% ≥ age 10 years; 33% and 50% FAB M4 and M5 | 11 | 22 |
| Other | 19 | 50% < age 2 years; 29% and 50% FAB M4 and M5, respectively | 39 | 54 | ||
| Normal karyotype | 20 | |||||
| Gene mutations | ||||||
| NPM | Nucleophosmin | Nuclear transporter RNA processing | 23 | 8%-10% of childhood AML | 65–80 | 75–85 |
| CEBPα | CCAAT/enhancer binding protein α | Transcription factor | 14 | 4%-6% of all childhood AML; more common in older patients, FAB M1 or M2 | 70 | 83 |
| FLT3/ALM | Fms-like tyrosine kinase 3 activation loop domain | Receptor for FLT3 | 3 | 6%-7% of all childhood AML | 50–60 | 60–70 |
| FLT3-ITD | Fms-like tyrosine kinase 3 internal tandem duplication | Receptor for FLT3 | 18 | 10%-15% of all childhood AML | < 35 | < 35 |
| WT1 | Wilms tumor 1 | Transcription factor | 13 | 8%-10% of all childhood AML | 22–35 | 35–56 |
| RAS | Rat sarcoma gene | Signal transduction | 3 | 5% of all childhood AML | ID | ID |
| PTPN11 | Protein tyrosine phosphatase, non-receptor type 11 | Tyrosine phosphatase | 2 | Most commonly associated with JMML | ID | ID |
| No known mutations | 24 | 40 | 50 | |||
| Poor-risk cytogenetics | < 15 | < 40 | < 40 | |||
| Del 5q/E5 | 1 | |||||
| −7 | 2 |
Abbreviations: AML, acute myeloid leukemia; EFS, event-free survival; ID, insufficient data; FAB, French-American-British; ATRA, all-trans-retinoic acid; JMML, juvenile myelomonocytic leukemia.