Cytogenetic and molecular genetic abnormalities conferring independent prognostic information in younger adults with AML
| Risk group . | Cytogenetic/molecular genetic abnormality . |
|---|---|
| Favorable | t(15;17)(q22;q21)/PML-RARA |
| t(8;21)(q22;q22)/RUNX1-RUNX1T1 | |
| inv(16)(p13q22)/t(16;16)(p13;q22)/CBFB-MYH11 | |
| NPM1 mutation (in absence of FLT3-ITD or DNMT3A mutation) | |
| Biallelic CEBPA mutation | |
| Intermediate | Cytogenetic/molecular genetic abnormalities not classified as favorable or adverse |
| Adverse | In the absence of favorable risk cytogenetic/molecular genetic abnormalities: |
| abn(3q) [excluding t(3;5)(q21∼25;q31∼35)/NPM1-MLF1], | |
| inv(3)(q21q26)/t(3;3)(q21;q26)/ GATA2/EVI1 | |
| add(5q)/del(5q), −5 | |
| t(5;11)(q35;p15.5)/NUP98-NSD1 | |
| t(6;9)(p23;q34)/DEK-NUP214 | |
| add(7q)/del(7q), −7 | |
| t(11q23) [excluding t(9;11)(p21∼22;q23) and t(11;19)(q23;p13)] | |
| t(9;22)(q34;q11)/BCR-ABL | |
| −17/abn(17p)/TP53 mutation | |
| Complex karyotype (≥4 unrelated abnormalities) | |
| ASXL1 mutation | |
| DNMT3A mutation | |
| FLT3-ITD | |
| MLL-PTD | |
| RUNX1 mutation |
| Risk group . | Cytogenetic/molecular genetic abnormality . |
|---|---|
| Favorable | t(15;17)(q22;q21)/PML-RARA |
| t(8;21)(q22;q22)/RUNX1-RUNX1T1 | |
| inv(16)(p13q22)/t(16;16)(p13;q22)/CBFB-MYH11 | |
| NPM1 mutation (in absence of FLT3-ITD or DNMT3A mutation) | |
| Biallelic CEBPA mutation | |
| Intermediate | Cytogenetic/molecular genetic abnormalities not classified as favorable or adverse |
| Adverse | In the absence of favorable risk cytogenetic/molecular genetic abnormalities: |
| abn(3q) [excluding t(3;5)(q21∼25;q31∼35)/NPM1-MLF1], | |
| inv(3)(q21q26)/t(3;3)(q21;q26)/ GATA2/EVI1 | |
| add(5q)/del(5q), −5 | |
| t(5;11)(q35;p15.5)/NUP98-NSD1 | |
| t(6;9)(p23;q34)/DEK-NUP214 | |
| add(7q)/del(7q), −7 | |
| t(11q23) [excluding t(9;11)(p21∼22;q23) and t(11;19)(q23;p13)] | |
| t(9;22)(q34;q11)/BCR-ABL | |
| −17/abn(17p)/TP53 mutation | |
| Complex karyotype (≥4 unrelated abnormalities) | |
| ASXL1 mutation | |
| DNMT3A mutation | |
| FLT3-ITD | |
| MLL-PTD | |
| RUNX1 mutation |
The cytogenetic classification is based on analysis of 5876 patients treated in successive United Kingdom national AML trials for younger adults.4 The cytogenetic adverse risk category captured virtually all patients (98%) with a monosomal karyotype, which characterizes a group of patients with dismal prognosis.101 Overall, of the 955 patients in the United Kingdom study with adverse risk disease based on cytogenetic criteria, 35% had a monosomal karyotype.4 There has been inconsistency in the definition of complex karyotype between studies.3 In the United Kingdom study, the most informative level of complexity was investigated to distinguish patients with poor prognosis AML with abnormal karyotype, lacking one of the cytogenetic changes that in their own right would have assigned a patient to the favorable or adverse risk group respectively.4 This analysis, which was restricted to patients with standard risk cytogenetic abnormalities, established that >3 unrelated abnormalities was the most informative cutoff for definition of “complex karyotype” to distinguish those with poor prognosis who should be assigned to the adverse risk group.4