Table 1.
Prevalence and prognosis of subtypes in B-ALL
| ALL subtype | Category | Median age (yr) | Prevalence | Genomic alterations | Clinical features | Reference(s) |
|---|---|---|---|---|---|---|
| Hyperdiploid (>50 chromosomes) | Aneuploid | 4 | High in children (25%) | Ras pathway Epigenetic modifiers | Excellent prognosis | Paulsson et al. 2015 |
| Low-hypodiploid (31–39 chromosomes) | Aneuploid | 47 | High in adults (10%–15%) | IKZF2 del, TP53 mut (commonly inherited) | Poor prognosis | Holmfeldt et al. 2013 |
| Near-haploid (24–30 chromosomes) | Aneuploid | 5.4 | <3% in all ages | Ras pathway, IKZF3 del | Intermediate prognosis | Holmfeldt et al. 2013 |
| iAMP21 | Copy number gain | 10 | ∼3% in children and AYA | Complex structural alterations of chromosome 21 | Good prognosis with intensive therapy, low WBC | Harrison 2015 |
| ETV6-RUNX1 t(12;21)(p13;q22) | TF rearrangement | 4 | High in children (25%) | PAX5 del, WHSC1 mut | Excellent prognosis | Mullighan et al. 2007; Jaffe et al. 2013 |
| ETV6-RUNX1-like | TF rearrangement | 3 | ∼3% in children | ETV6 fusions and del, IKZF1 fusions and del | Unknown | Lilljebjörn et al. 2016; Zaliova et al. 2017 |
| DUX4-rearranged | TF rearrangement | 14.3 | Peak in AYA (∼8%) | ERG del, IKZF1 del, Ras pathway | Excellent prognosis | Lilljebjörn et al. 2016; Yasuda et al. 2016; Zhang et al. 2016 |
| KMT2A-rearranged | TF rearrangement | 40 | High in infants (∼90%) and adults (∼15%) | Ras pathway (commonly subclonal) | Poor prognosis, sensitive to bortezomib or DOT1L inhibition | Andersson et al. 2015 |
| TCF3-PBX1 t(1;19)(q23;p13) | TF rearrangement | 8 | ∼5% in children, rarely in adults | Good prognosis, CNS relapse | Barber et al. 2007; Burmeister et al. 2010 | |
| ZNF384-rearranged | TF rearrangement | 15 | Peak in AYA (∼5%) | Epigenetic modifiers, Ras pathway | Intermediate prognosis | Liu et al. 2016; Shago et al. 2016; Yasuda et al. 2016 |
| MEF2D-rearranged | TF rearrangement | 14 | Peak in AYA (∼7%) | Ras pathway | Intermediate prognosis, sensitive to HDAC inhibition | Gu et al. 2016; Suzuki et al. 2016 |
| NUTM1-rearranged | TF rearrangement | 3 | Exclusively in children (1%) | Unknown | Excellent prognosis | Li et al. 2018; Gu et al. 2019 |
| TCF3-HLF t(17;19)(q22;p13) | TF rearrangement | 15 | Very rare in all ages (<1%) | TCF3 mut, PAX5 del, Ras pathway | Very poor prognosis, sensitive to Bcl2 inhibition | Fischer et al. 2015 |
| PAX5alt | Other TF-driven | 10 | Highest in children (∼11%) | PAX5 fusion, mut, amp | Intermediate prognosis | Li et al. 2018; Gu et al. 2019 |
| PAX5 P80R | Other TF-driven | 22 | Highest in adults (∼4%) | Ras pathway | Intermediate prognosis | Li et al. 2018; Gu et al. 2019 |
| IKZF1 N159Y | Other TF-driven | Very rare in all ages (<1%) | Unknown | Unknown | Li et al. 2018; Gu et al. 2019 | |
| BCL2/MYC-rearranged | Other TF-driven | 48 | Almost exclusively in AYA and adults (∼3%) | Unknown | Poor prognosis | Gu et al. 2019 |
| Ph-like | Kinase-driven | 21 | Peaks in AYA (25%–30%) | Multiple kinase alterations, IKZF1 del and mut, CDKN2A/B del | Poor prognosis, amenable to TKI therapy | Roberts et al. 2014a, 2017a |
| BCR-ABL1 t(9;22)(q34;q11.2) | Kinase-driven | 40–45 | 5% in children, highest in adults (40%–50%) | IKZF1 del and mut, CDKN2A/B del | Historically poor prognosis, improved with TKI | Mullighan et al. 2008a; Roberts et al. 2014a, 2017a |
| Other | 16 | ∼5% in children, ∼10% in AYA and adults | Unknown | Intermediate prognosis |
(AYA) Adolescent and young adult, (amp) amplification, (B-ALL) B-progenitor acute lymphoblastic leukemia, (CNS) central nervous system, (del) deletion, (HDAC) histone deacetylase, (mut) sequence mutation, (TF) transcription factor, (TKI) tyrosine kinase inhibitor.