ALL Subtypes

The subtypes of ALL are identified based on certain features of the leukemia cells. Determining the ALL subtype is an important factor in treatment planning. The doctor will discuss with you which drug combinations are indicated based on your child’s ALL subtype.

Leukemia cells can be classified by the unique set of proteins found on their surface. These unique sets of proteins are known as “immunophenotypes.” Based on immunophenotyping of the leukemia cell, the World Health Organization (WHO) classifies ALL into two main subtypes.

  • B-cell lymphoblastic leukemia/lymphoma: This subtype begins in immature cells that would normally develop into B-cell lymphocytes. B-cell ALL is the most common ALL subtype, accounting for approximately 80 percent of cases among children with ALL.
  • T-cell lymphoblastic leukemia: This subtype of ALL originates in immature cells that would normally develop into T-cell lymphocytes. This subtype is less common than B-cell ALL and occurs more often in adults than in children. T-cell ALL accounts for approximately 15 to 20 percent of ALL cases in children.

Genetic Changes

In addition to classifying ALL as either B-cell or T-cell, it can be further classified based on changes to certain chromosomes and genes.

Not all patients who have ALL exhibit the same genetic changes. Some changes are more common than others, and some have a greater effect on the patient’s prognosis.

Philadelphia Chromosome-Positive ALL. About 2 to 4 percent of children with ALL have a subtype called Philadelphia chromosome-positive ALL (also known as “Ph+ ALL” or “Ph-positive ALL”). The leukemia cells of these patients have the Philadelphia chromosome, which is formed by a translocation between parts of chromosomes 9 and 22. The new, abnormal chromosome 22 is known as the Philadelphia chromosome. This chromosomal alteration creates a gene called BCR-ABL1. This gene produces a protein called a tyrosine kinase, which causes the leukemia cells to grow and divide out of control.

Philadelphia Chromosome-like (Ph-like) ALL. About 15 percent of children with ALL have a subtype of B-cell ALL called “Ph-like ALL.” This is a high-risk subtype of ALL in children that seems to peak in adolescents and young adults and is more likely to be seen in males and patients with Down syndrome. It is associated with an unfavorable prognosis. Ph-like ALL has genetic features similar to Ph+ ALL, but without the BCR-ABL1 fusion gene that defines Ph+ ALL. Instead, patients have a highly diverse range of genetic mutations that activate tyrosine kinase signaling.

Prognostic Factors 

Children with ALL are often categorized into one of three risk groups — standard risk, high risk, or very high risk — based on prognostic factors. This is called risk stratification. Typically, children with ALL in the low-risk group have a better prognosis and receive less intensive treatment than those in the two higher-risk groups.

Prognostic factors for children with ALL include:

  • Age: ALL tends to be more aggressive in infants younger than 1 year and children older than 10 years.
  • White blood cell count: Children with white blood cell counts of 50,000 per microliter or greater at the time of diagnosis need stronger treatment. 
  • Biomarkers: Certain changes in the chromosomes or genes can make the leukemia cells either easier or harder to treat. These changes help determine whether your child may benefit from treatment with more intensive therapies. Researchers have found that for patients with B-cell ALL, some genetic mutations respond better to treatment than others. Identifying specific genetic abnormalities for patients with B-cell ALL is critical for disease evaluation, risk stratification and treatment planning.
  • Extramedullary disease: Children with ALL who have leukemia cells in the central nervous system or testicles at diagnosis are at a higher risk of disease relapse.
  • Treatment response: Children who have a better response to the initial induction therapy have a lower risk of disease relapse. For children with T-cell ALL, risk stratification is primarily based on their early treatment response.

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