Prevalence and prognosis of subtypes in Ba-ALL
| ALL subtype . | Category . | Median age, y . | Prevalence . | Genomic alterations . | Clinical features . | References . | |
|---|---|---|---|---|---|---|---|
| Hyperdiploid (>50 chromosomes) | Aneuploid | 4 | High in children (25%) | Ras pathway, epigenetic modifiers | Excellent prognosis | 9 | |
| Low hypodiploid (31-39 chromosomes) | Aneuploid | 47 | High in adults (10%-15%) | IKZF2 del, TP53 mut (commonly inherited) | Poor prognosis | 10 | |
| Near haploid (24-30 chromosomes) | Aneuploid | 5 | <3% in all ages | Ras pathway, IKZF3 del | Intermediate prognosis | 10 | |
| iAMP21 | Copy number gain | 10 | ∼3% in children and AYAs | Complex structural alterations of chromosome 21 | Good prognosis with intensive therapy, low WBC | 12 | |
| ETV6-RUNX1 t(12;21)(p13;q22) | TF rearrangement | 4 | High in children (25%) | PAX5 del, WHSC1 mut | Excellent prognosis | 8,13 | |
| ETV6-RUNX1 like | TF rearrangement | 3 | ∼3% in children | ETV6 fusions and del, IKZF1 fusions and del | Unknown | 34,35 | |
| DUX4 rearranged | TF rearrangement | 14 | Peak in AYAs (∼8%) | ERG del, IKZF1 del, Ras pathway | Excellent prognosis | 34,36,37 | |
| KMT2A rearranged | TF rearrangement | 40 | High in infants (∼90%) and adults (∼15%) | Ras pathway (commonly subclonal) | Poor prognosis, sensitive to bortezomib or DOT1L inhibition | 14 | |
| TCF3-PBX1 t(1;19)(q23;p13) | TF rearrangement | 8 | ∼5% in children, rarely in adults | Good prognosis, CNS relapse | 15,16 | ||
| ZNF384 rearranged | TF rearrangement | 15 | Peak in AYAs (∼5%) | Epigenetic modifiers, Ras pathway | Intermediate prognosis | 36,41,42 | |
| MEF2D rearranged | TF rearrangement | 14 | Peak in AYAs (∼7%) | Ras pathway | Intermediate prognosis, sensitive to HDAC inhibition | 39,40 | |
| NUTM1 rearranged | TF rearrangement | 3 | Exclusively in children (1%) | Unknown | Excellent prognosis | ||
| 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 | 17 | |
| PAX5alt | Other TF driven | 10 | Highest in children (∼11%) | PAX5 fusion, mut, amp | Intermediate prognosis | ||
| PAX5 P80R | Other TF driven | 22 | Highest in adults (∼4%) | Signaling alterations | Unclear | ||
| BCL2/MYC rearranged | Other TF driven | 48 | Almost exclusively in AYAs and adults (∼3%) | Unknown | Poor prognosis | ||
| Ph-like | Kinase driven | 21 | Peaks in AYAs (25%-30%) | Multiple kinase alterations, IKZF1 del and mut, CDKN2A/B del | Poor prognosis, amenable to TKI therapy | 18,19 | |
| 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 | 18,19,23 | |
| Other | 16 | ∼5% children; ∼10% AYAs and adults | Unknown | Intermediate prognosis |
| ALL subtype . | Category . | Median age, y . | Prevalence . | Genomic alterations . | Clinical features . | References . | |
|---|---|---|---|---|---|---|---|
| Hyperdiploid (>50 chromosomes) | Aneuploid | 4 | High in children (25%) | Ras pathway, epigenetic modifiers | Excellent prognosis | 9 | |
| Low hypodiploid (31-39 chromosomes) | Aneuploid | 47 | High in adults (10%-15%) | IKZF2 del, TP53 mut (commonly inherited) | Poor prognosis | 10 | |
| Near haploid (24-30 chromosomes) | Aneuploid | 5 | <3% in all ages | Ras pathway, IKZF3 del | Intermediate prognosis | 10 | |
| iAMP21 | Copy number gain | 10 | ∼3% in children and AYAs | Complex structural alterations of chromosome 21 | Good prognosis with intensive therapy, low WBC | 12 | |
| ETV6-RUNX1 t(12;21)(p13;q22) | TF rearrangement | 4 | High in children (25%) | PAX5 del, WHSC1 mut | Excellent prognosis | 8,13 | |
| ETV6-RUNX1 like | TF rearrangement | 3 | ∼3% in children | ETV6 fusions and del, IKZF1 fusions and del | Unknown | 34,35 | |
| DUX4 rearranged | TF rearrangement | 14 | Peak in AYAs (∼8%) | ERG del, IKZF1 del, Ras pathway | Excellent prognosis | 34,36,37 | |
| KMT2A rearranged | TF rearrangement | 40 | High in infants (∼90%) and adults (∼15%) | Ras pathway (commonly subclonal) | Poor prognosis, sensitive to bortezomib or DOT1L inhibition | 14 | |
| TCF3-PBX1 t(1;19)(q23;p13) | TF rearrangement | 8 | ∼5% in children, rarely in adults | Good prognosis, CNS relapse | 15,16 | ||
| ZNF384 rearranged | TF rearrangement | 15 | Peak in AYAs (∼5%) | Epigenetic modifiers, Ras pathway | Intermediate prognosis | 36,41,42 | |
| MEF2D rearranged | TF rearrangement | 14 | Peak in AYAs (∼7%) | Ras pathway | Intermediate prognosis, sensitive to HDAC inhibition | 39,40 | |
| NUTM1 rearranged | TF rearrangement | 3 | Exclusively in children (1%) | Unknown | Excellent prognosis | ||
| 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 | 17 | |
| PAX5alt | Other TF driven | 10 | Highest in children (∼11%) | PAX5 fusion, mut, amp | Intermediate prognosis | ||
| PAX5 P80R | Other TF driven | 22 | Highest in adults (∼4%) | Signaling alterations | Unclear | ||
| BCL2/MYC rearranged | Other TF driven | 48 | Almost exclusively in AYAs and adults (∼3%) | Unknown | Poor prognosis | ||
| Ph-like | Kinase driven | 21 | Peaks in AYAs (25%-30%) | Multiple kinase alterations, IKZF1 del and mut, CDKN2A/B del | Poor prognosis, amenable to TKI therapy | 18,19 | |
| 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 | 18,19,23 | |
| Other | 16 | ∼5% children; ∼10% AYAs and adults | Unknown | Intermediate prognosis |
ALL, acute lymphoblastic leukemia; amp, amplification; AYA, adolescent and young adult; CNS, central nervous system; del, deletion; DUX4, double homeobox 4; ERG, ETS transcription factor; HDAC, histone deacetylase; iAMP21, intrachromosomal amplification of chromosome 21; MEF2D, myocyte enhancer factor 2D; mut, sequence mutation; NUTM1, nuclear protein in testis midline carcinoma family 1; Ph like, Philadelphia chromosome like; TF, transcription factor; TKI, tyrosine kinase inhibitor; WBC, white blood cell; ZNF384, zinc finger 384.