Types

Updated May 9, 2024

The World Health Organization (WHO) classification system is the most commonly used method to distinguish acute lymphoblastic leukemia subtypes.¹

Classification¹

Based on the type of white blood cell (lymphocyte) affected, two main subtypes can be found:

B-cell acute lymphoblastic leukemia, which is the most common type (75% of cases in adults; 80-85% of cases in children)²

• Most B-cell acute lymphoblastic leukemia stems from abnormal immature (pre) B cells.
• Sometimes B-cell acute lymphoblastic leukemia develops from malignant mature B cells. You may also hear it called Burkitt-type acute lymphoblastic leukemia, as it is similar to another type of cancer called Burkitt lymphoma.²

T-cell acute lymphoblastic leukemia (25% of cases in adults; 15% of cases in children)²

More frequent in young adults and in men.

Further classification

Leukemia subtypes can be further categorized into around 25 different subtypes according to the genetic abnormalities present. These genetic subtypes are very important for patient management, helping doctors to confirm a diagnosis and select the optimal treatment pathway; some genetic subtypes indicate that the disease will respond to a specific drug while others can indicate the aggressiveness of the leukemia. Doctors will use the genetic subtype in combination with other factors, like age and response to treatment, to determine the level of chemotherapy required by each patient.

The frequency of genetic subtypes varies by patient age and time of diagnosis.

B-cell acute lymphoblastic leukemia

Philadelphia-positive acute lymphoblastic leukemia

The most common genetic abnormality in adult acute lymphoblastic leukemia is the formation of the Philadelphia (Ph) chromosome; this is caused by the exchange of genetic material between Chromosomes 9 and 22 in leukemic cells, resulting in the creation of the BCR::ABL1 fusion gene. The presence of this fusion gene confers a sensitivity to a class of drug called tyrosine kinase inhibitors. Ph-positive acute lymphoblastic leukemia occurs in 25% of adults,² but only 3-4% of children.⁴ You can read more about this and other therapies on the treatment page.⁴

Philadelphia-like acute lymphoblastic leukemia⁵

Characterized by a similar gene expression profile to Ph-positive acute lymphoblastic leukemia but lacking the BCR::ABL1 gene fusion. Although Ph-like acute lymphoblastic leukemia can occur at any age, it most frequently occurs in adolescents and adults. This subtype comprises two subgroups: ABL1 class fusions and JAK-STAT abnormality. The presence of an ABL-class fusion, but not a JAK-STAT abnormality, confers a sensitivity to a type of drug called tyrosine kinase inhibitors, making these drugs more effective.

ETV6::RUNX1 fusion or t(12;21)(p13;q21) acute lymphoblastic leukemia⁴

This is a common genetic abnormality in children with acute lymphoblastic leukemia, occurring in ~25% of cases; however, it is very rare in adults. Children with ETV6::RUNX1-positive acute lymphoblastic leukemia generally have good outcomes.

High hyperpdiploid acute lymphoblastic leukemia

This is the most common genetic abnormality in children with acute lymphoblastic leukemia, occurring in 30% of cases and only occurring in around 10% of adults. It is characterized by the multiple gain of whole chromosomes. Most children with high hyperdiploid acute lymphoblastic leukemia have a favourable prognosis.

KMT2A or MLL gene fusion acute lymphoblastic leukemia⁴

Abnormalities involving the KMT2A gene can occur at any age and are usually associated with aggressive disease. Around 80% of infant patients (aged <1 year) will have this genetic subtype. It is rare in children (5%) but starts to increase in frequency with age—accounting for around 10% of adults with acute lymphoblastic leukemia.

Hypodiploidy acute lymphoblastic leukemia⁴

This genetic subtype is characterized by multiple chromosome losses and associated with aggressive disease. There are two subgroups: near haploidy and low hypodiploidy. Both subgroups are rare in children, accounting for ~6% of cases. Near haploid acute lymphoblastic leukemia is extremely rare in adults, but low hypodiploidy occurs in ~6%, especially in older patients (aged >50 years).

iAMP21 acute lymphoblastic leukemia⁴

This genetic subtype involves a very complex rearrangement of Chromosome 21 and gives rise to an aggressive form of the disease. It most frequently occurs in older children (aged 8–14 years) and is rare in other age groups.

ABL-class gene fusion acute lymphoblastic leukemia⁴

This genetic subtype comprises a series of gene fusions involving one of the following genes: ABL1, ABL2, CSF1R, and PDGFRB. Similar to patients with the BCR::ABL1 fusion gene, these patients are usually sensitive to tyrosine kinase inhibitors, with many patients treated with imatinib or dasatinib, alongside standard chemotherapy. This genetic subtype is quite rare, accounting for 3–4% of cases in children.

Other B-cell acute lymphoblastic leukemia subtypes include t(5;14)(q31.1;q32.3)/IGH::IL3, t(1;19)(q23.3;p13.3)/TCF3::PBX1, TCF3::HLF fusion, MYC rearrangement, DUX4 rearrangement, MEF2D rearrangement, ZNF384(362) rearrangement, NUTM1 rearrangement, CDX2/UBTF, IKZF1 N159Y mutation, ETV6::RUNX1-like, PAX5 alteration, ZEB2 (p.H1038R) mutation/IGH::CEBPE, ZNF384-like, and KMT2A-like.

T-cell acute lymphoblastic leukemia

T-cell acute lymphoblastic leukemia can be further classified according to both immunophenotype and genetics. Whilst many subtypes have been described in the research literature, the clinical relevance and prognostic value are not well understood. Further research is needed before these subtypes are widely and consistently used in the clinical setting.

This list of genetic subtypes is not exhaustive, we have focused on the most common subtypes used by doctors to make treatment decisions. The official classification of acute lymphoblastic leukemia can be found in the WHO classification.¹