Molecular subgroups in adult ALL: incidence, prognosis, and molecular findings
| ALL subset . | Prevalence and prognosis∗ . | Related aberration(s) . |
|---|---|---|
| B-lineage ALL | ||
| BCR::ABL1/t(9;22)(q34;q11.2) (Ph+) | 20%-50%, increasing with age; improved by tyrosine kinase inhibitor therapy | BCR::ABL1 rearrangement |
| Ph-like | 25%-27% Unfavorable/controversial for current regimens | Gene expression profile like BCR::ABL1+ ALL but without BCR::ABL1 rearrangement |
| TCF3::PBX1/t(1;19)(q23;p13) | 10%-15% Favorable with intensive therapy | TCF3::PBX1 rearrangement |
| KMT2A(MLL)::AFF1/t(4;11)(q21;q23.3), KMT2A-rearranged/t(v;11q23.3) | ∼5% Unfavorable | KMT2A::AFF1 or KMT2A-other partner gene rearrangement |
| IGH::MYC/t(8,14)(q24;q32) | 1%-5% Unfavorable in B-precursor ALL | IGH::MYC rearrangement |
| TCF3::HLF/t(17;19)(q22;p13.3) | <1% Unfavorable | TCF3::HLF rearrangement |
| iAMP21 | ∼2% Intermediate/unfavorable | — |
| 14q32 translocations | <5%, higher in adolescents Intermediate/unfavorable | IGH fusion with partner genes CRLF2, ID4, CEBP, BCL2, EPOR, LHX4, and IL-3 |
| 9p13 deletions/translocations | ∼25% No impact on outcome | PAX5 fusion with partner genes ETV6, ELN, POM121, PML, FOXP1, MLLT3, JAK2, C20orf112, AUTS2, CHFR, SOX5, and POM121C |
| 7p12.2 focal deletions/mutations | 50%; 80% in Ph+ and Ph–like Controversial prognosis | Deletions of IKZF1 |
| DUX4-rearranged and ERG-deregulated | 3%-7% Favorable | ERG and IKZF1 deletions |
| MEF2D-rearranged ALL | 3%-4% Poor | |
| ZNF384-rearranged ALL | 6%-7% Intermediate | Partner gene EP300, CREBBP, TAF15, SYNRG, EWSR1, TCF3, and ARID1B |
| CDX2::UBTF | 2.7%-4% Poor | High expression of CDX2 and gain (1q); UBTF::ATXN7L3; CDX2-cis-deregulation |
| T-lineage ALL | ||
| TAL and LMO rearrangements/del(1)(p32), t(1;14)(p32;q11), t(1;7)(p32;q34), t(7;9)(q34;q32), t(11;14)(p15;q1), t(11;14)(p13;q1), t(7;11)(q35;p13) | 30%-40% Favorable and partly depending on additional lesions | SIL-TAL1 rearrangement, TCR rearrangements with TAL1, TAL2, LMO1, and LMO2 |
| HOXA aberrations/inv(7)(p15q34), t(7;7)(p15;q34), t(10;11)(p13;q14), t(v;11q23), del(9)(q34) | 20%-25% Outcome depending on additional lesions | TCR-HOXA rearrangement, MLLT10 and MLL rearrangements with various partners, SET-NUP214 rearrangement |
| TLX1-10q24 rearrangements/t(7;10)(q34;q24), t(10;14)(q24;q11) | 20%-30% No impact on prognosis | TCR-TLX11 rearrangement |
| ETP ALL | 10%-15% Unfavorable/controversial | Deregulation of myeloid transcription factors, of members of RAS pathway and of epigenetic regulators |
| TLX3-5q35 rearrangement/t(5;14)(q35;q32) | 10% No impact on prognosis | TLX3-BCL11B rearrangement |
| t(8;14)(q24;q11) | 1% Unfavorable | MYC involvement |
| ABL1 rearrangements | ∼3% Potentially targetable by tyrosine kinase inhibitors | NUP214, EML1; ETV6 |
| LYL/MEF2C rearrangement and immature cluster/t(7;19)(q34;p13), del(5)(q14) | 3%-17% Unfavorable; improved by intensive treatment | TCR with LYL1 MEF2C rearrangements |
| NKX2-1/NKX2-2 rearrangements/inv(14)(q11.2q13), t(7;14)(q34;q13), inv(14)(q13q32.33), t(14;20)(q11;p11) | 6% No impact on prognosis | TCR/IGH-NKX2- or NKX2-2 rearrangements |
| ALL subset . | Prevalence and prognosis∗ . | Related aberration(s) . |
|---|---|---|
| B-lineage ALL | ||
| BCR::ABL1/t(9;22)(q34;q11.2) (Ph+) | 20%-50%, increasing with age; improved by tyrosine kinase inhibitor therapy | BCR::ABL1 rearrangement |
| Ph-like | 25%-27% Unfavorable/controversial for current regimens | Gene expression profile like BCR::ABL1+ ALL but without BCR::ABL1 rearrangement |
| TCF3::PBX1/t(1;19)(q23;p13) | 10%-15% Favorable with intensive therapy | TCF3::PBX1 rearrangement |
| KMT2A(MLL)::AFF1/t(4;11)(q21;q23.3), KMT2A-rearranged/t(v;11q23.3) | ∼5% Unfavorable | KMT2A::AFF1 or KMT2A-other partner gene rearrangement |
| IGH::MYC/t(8,14)(q24;q32) | 1%-5% Unfavorable in B-precursor ALL | IGH::MYC rearrangement |
| TCF3::HLF/t(17;19)(q22;p13.3) | <1% Unfavorable | TCF3::HLF rearrangement |
| iAMP21 | ∼2% Intermediate/unfavorable | — |
| 14q32 translocations | <5%, higher in adolescents Intermediate/unfavorable | IGH fusion with partner genes CRLF2, ID4, CEBP, BCL2, EPOR, LHX4, and IL-3 |
| 9p13 deletions/translocations | ∼25% No impact on outcome | PAX5 fusion with partner genes ETV6, ELN, POM121, PML, FOXP1, MLLT3, JAK2, C20orf112, AUTS2, CHFR, SOX5, and POM121C |
| 7p12.2 focal deletions/mutations | 50%; 80% in Ph+ and Ph–like Controversial prognosis | Deletions of IKZF1 |
| DUX4-rearranged and ERG-deregulated | 3%-7% Favorable | ERG and IKZF1 deletions |
| MEF2D-rearranged ALL | 3%-4% Poor | |
| ZNF384-rearranged ALL | 6%-7% Intermediate | Partner gene EP300, CREBBP, TAF15, SYNRG, EWSR1, TCF3, and ARID1B |
| CDX2::UBTF | 2.7%-4% Poor | High expression of CDX2 and gain (1q); UBTF::ATXN7L3; CDX2-cis-deregulation |
| T-lineage ALL | ||
| TAL and LMO rearrangements/del(1)(p32), t(1;14)(p32;q11), t(1;7)(p32;q34), t(7;9)(q34;q32), t(11;14)(p15;q1), t(11;14)(p13;q1), t(7;11)(q35;p13) | 30%-40% Favorable and partly depending on additional lesions | SIL-TAL1 rearrangement, TCR rearrangements with TAL1, TAL2, LMO1, and LMO2 |
| HOXA aberrations/inv(7)(p15q34), t(7;7)(p15;q34), t(10;11)(p13;q14), t(v;11q23), del(9)(q34) | 20%-25% Outcome depending on additional lesions | TCR-HOXA rearrangement, MLLT10 and MLL rearrangements with various partners, SET-NUP214 rearrangement |
| TLX1-10q24 rearrangements/t(7;10)(q34;q24), t(10;14)(q24;q11) | 20%-30% No impact on prognosis | TCR-TLX11 rearrangement |
| ETP ALL | 10%-15% Unfavorable/controversial | Deregulation of myeloid transcription factors, of members of RAS pathway and of epigenetic regulators |
| TLX3-5q35 rearrangement/t(5;14)(q35;q32) | 10% No impact on prognosis | TLX3-BCL11B rearrangement |
| t(8;14)(q24;q11) | 1% Unfavorable | MYC involvement |
| ABL1 rearrangements | ∼3% Potentially targetable by tyrosine kinase inhibitors | NUP214, EML1; ETV6 |
| LYL/MEF2C rearrangement and immature cluster/t(7;19)(q34;p13), del(5)(q14) | 3%-17% Unfavorable; improved by intensive treatment | TCR with LYL1 MEF2C rearrangements |
| NKX2-1/NKX2-2 rearrangements/inv(14)(q11.2q13), t(7;14)(q34;q13), inv(14)(q13q32.33), t(14;20)(q11;p11) | 6% No impact on prognosis | TCR/IGH-NKX2- or NKX2-2 rearrangements |
Any prognostic statements should be considered carefully; because they depend on protocol, presence of other prognostic features, and are often based on small patient numbers.