Key subtypes of ALL
| Subtype . | Prevalence (%)* . | Comment . |
|---|---|---|
| B-cell precursor ALL | ||
| Hyperdiploidy with >50 chromosomes | 20-30 | Excellent prognosis |
| Hypodiploidy with <44 chromosomes | 2-3 | Poor prognosis; high frequency of Ras pathway and Ikaros gene family mutations |
| t(12;21)(p13;q22) translocation encoding ETV6-RUNX1 | 15-25 | Excellent prognosis |
| t(1;19)(q23;p13) translocation encoding TCF3-PBX1 | 2-6 | Increased incidence in African-Americans; generally excellent prognosis; association with CNS relapse |
| t(9;22)(q34;q11.2) translocation encoding BCR-ABL1 | 2-4 | Historically poor outcome; improved with addition of imatinib and/or dasatinib to intensive chemotherapy |
| Ph-like ALL | 10-15 | Multiple kinase-activating lesions; associated with older age, elevated white blood cell count, and IKZF1 alteration; potentially amenable to TKI therapy |
| t(4;11)(q21;q23) translocation encoding MLL-AF4 fusion | 1-2 | Common in infant ALL (especially age <6 mo); poor prognosis |
| t(8;14)(q24;q32), t(2;8)(q12;q24), t(2;8)(q12;q24) encoding; MYC rearrangement | 2 | Favorable prognosis with short-term high-dose chemotherapy |
| CRLF2 rearrangement (IGH-CRLF2; P2RY8-CRLF2) | 5-7 | Common in Down syndrome–associated and Ph-like ALL (∼50% each); associated with IKZF1 deletion and/or mutation and JAK1/2 mutation and poor prognosis in non–Down syndrome–associated ALL |
| ERG-dysregulated ALL | ∼7 | Distinct gene expression profile; the majority have focal ERG deletions and favorable outcome despite IKZF1 alterations |
| PAX5 rearrangement | ∼2 | Multiple partners, commonly from dic(7;9), dic(9;12), and dic(9;20) |
| iAMP21 | ∼2 | Complex structural alterations of chromosome 21; rarely associated with a constitutional Robertsonian translocation rob(15;21)(q10;q10)c; poor prognosis |
| T-lineage ALL | ||
| t(1;7)(p32;q35) and t(1;14)(p32;q11) translocations and interstitial 1p32 deletion; TAL1 dysregulation | 15-18 | Generally favorable outcome |
| t(11;14)(p15;q11) translocation and 5′ LMO2 deletion; LMO2 dysregulation | 10 | Generally favorable outcome |
| t(10;14)(q24;q11) and t(7;10)(q35;q24) translocations; TLX1 [HOX11] dysregulation | 7 | Good prognosis |
| t(5;14)(q35;q32) translocation; TLX3 dysregulation | 20 | Commonly fused to BCL11B, also a target of deletion and/or mutation; poor prognosis |
| t(10;11)(p13;q14) translocation; PICALM-MLLT10 [CALM-AF10] | 10 | May have poor outcome |
| MLL-MLLT1 [MLL-ENL] | 2-3 | Superior prognosis to other types of MLL-rearranged leukemia |
| 9q34 amplification encoding NUP214-ABL1 | 6 | Potentially amenable to TKIs, also identified in high-risk B-ALL; other kinase fusions identified in T-ALL include EML1-ABL1, ETV6-JAK2, and ETV6-ABL1 |
| t(7;9)(q34;q34) translocation | <1 | Rearrangement of NOTCH1; also sequence mutations in >50% T-ALL |
| Early T-cell precursor ALL | 10-15 | Immature immunophenotype; expression of myeloid and/or stem cell markers; historically poor outcome, although improved in recent studies; genetically heterogeneous with mutations in hematopoietic regulators, cytokine, and Ras signaling, and epigenetic modifiers |
| Subtype . | Prevalence (%)* . | Comment . |
|---|---|---|
| B-cell precursor ALL | ||
| Hyperdiploidy with >50 chromosomes | 20-30 | Excellent prognosis |
| Hypodiploidy with <44 chromosomes | 2-3 | Poor prognosis; high frequency of Ras pathway and Ikaros gene family mutations |
| t(12;21)(p13;q22) translocation encoding ETV6-RUNX1 | 15-25 | Excellent prognosis |
| t(1;19)(q23;p13) translocation encoding TCF3-PBX1 | 2-6 | Increased incidence in African-Americans; generally excellent prognosis; association with CNS relapse |
| t(9;22)(q34;q11.2) translocation encoding BCR-ABL1 | 2-4 | Historically poor outcome; improved with addition of imatinib and/or dasatinib to intensive chemotherapy |
| Ph-like ALL | 10-15 | Multiple kinase-activating lesions; associated with older age, elevated white blood cell count, and IKZF1 alteration; potentially amenable to TKI therapy |
| t(4;11)(q21;q23) translocation encoding MLL-AF4 fusion | 1-2 | Common in infant ALL (especially age <6 mo); poor prognosis |
| t(8;14)(q24;q32), t(2;8)(q12;q24), t(2;8)(q12;q24) encoding; MYC rearrangement | 2 | Favorable prognosis with short-term high-dose chemotherapy |
| CRLF2 rearrangement (IGH-CRLF2; P2RY8-CRLF2) | 5-7 | Common in Down syndrome–associated and Ph-like ALL (∼50% each); associated with IKZF1 deletion and/or mutation and JAK1/2 mutation and poor prognosis in non–Down syndrome–associated ALL |
| ERG-dysregulated ALL | ∼7 | Distinct gene expression profile; the majority have focal ERG deletions and favorable outcome despite IKZF1 alterations |
| PAX5 rearrangement | ∼2 | Multiple partners, commonly from dic(7;9), dic(9;12), and dic(9;20) |
| iAMP21 | ∼2 | Complex structural alterations of chromosome 21; rarely associated with a constitutional Robertsonian translocation rob(15;21)(q10;q10)c; poor prognosis |
| T-lineage ALL | ||
| t(1;7)(p32;q35) and t(1;14)(p32;q11) translocations and interstitial 1p32 deletion; TAL1 dysregulation | 15-18 | Generally favorable outcome |
| t(11;14)(p15;q11) translocation and 5′ LMO2 deletion; LMO2 dysregulation | 10 | Generally favorable outcome |
| t(10;14)(q24;q11) and t(7;10)(q35;q24) translocations; TLX1 [HOX11] dysregulation | 7 | Good prognosis |
| t(5;14)(q35;q32) translocation; TLX3 dysregulation | 20 | Commonly fused to BCL11B, also a target of deletion and/or mutation; poor prognosis |
| t(10;11)(p13;q14) translocation; PICALM-MLLT10 [CALM-AF10] | 10 | May have poor outcome |
| MLL-MLLT1 [MLL-ENL] | 2-3 | Superior prognosis to other types of MLL-rearranged leukemia |
| 9q34 amplification encoding NUP214-ABL1 | 6 | Potentially amenable to TKIs, also identified in high-risk B-ALL; other kinase fusions identified in T-ALL include EML1-ABL1, ETV6-JAK2, and ETV6-ABL1 |
| t(7;9)(q34;q34) translocation | <1 | Rearrangement of NOTCH1; also sequence mutations in >50% T-ALL |
| Early T-cell precursor ALL | 10-15 | Immature immunophenotype; expression of myeloid and/or stem cell markers; historically poor outcome, although improved in recent studies; genetically heterogeneous with mutations in hematopoietic regulators, cytokine, and Ras signaling, and epigenetic modifiers |
CNS, central nervous system.
Frequencies refer to childhood ALL.