What Causes Acute Lymphocytic Leukemia (ALL)?

Most people with ALL (acute lymphocytic leukemia, also known as acute lymphoblastic leukemia) have one or more known risk factors. But even when a person has one or more risk factors for ALL, it can be very hard to know if this actually caused the leukemia.

We still don’t know what causes ALL in most people. But researchers are beginning to understand how gene and chromosome changes may play a role.

How gene changes can lead to leukemia

Genes are the instructions inside each cell in your body that control how those cells function. They are made up of DNA and are inherited from both of your parents.

Different genes have different functions in our bodies. When they work properly, certain genes:

• Help control when our cells grow and divide to make new cells
• Repair mistakes in our DNA
• Cause cells to die when they’re damaged or no longer needed

But sometimes, changes (mutations) can happen in these genes, which can stop them from working the way they should. This might cause the cells to grow out of control, which can lead to cancer. To learn more, see Oncogenes, Tumor Suppressor Genes, and DNA Repair Genes.

When these types of gene changes happen in cells in the bone marrow (where new blood cells are made) it sometimes leads to ALL or another type of leukemia.

Gene and chromosome changes in ALL cells

The DNA inside each cell is in long strands called chromosomes. Each time a cell divides into 2 new cells, it must make a new copy of its chromosomes. This process isn't perfect. Sometimes errors happen that affect genes within the chromosomes.

• Mutations in many different genes can be found in ALL cells.
• Larger changes in one or more chromosomes are also common.

Even though chromosome changes involve large pieces of DNA, the problems that happen because of these changes are most likely caused by mutations in just 1 (or possibly a few) genes on that chromosome.

Several types of chromosome changes might be found in ALL cells.

Chromosome translocations

Translocations are the most common type of chromosome change that can lead to leukemia.

A translocation means DNA from one chromosome breaks off and becomes attached to a different chromosome. The point on the chromosome where the break happens can affect nearby genes. For example, it can turn on genes that help cells grow (oncogenes) or turn off genes that normally help a cell mature (tumor suppressor genes).

Philadelphia chromosome

The most common translocation in ALL in adults is known as the Philadelphia chromosome. This is a swap of DNA between chromosomes 9 and 22, abbreviated as t(9;22). It leads to the creation of the BCR::ABL1 oncogene.

Less common translocations

Many other, less common translocations can happen as well, including those between chromosomes 4 and 11, t(4;11); 12 and 21, t(12;21); or 1 and 19, t(1;19).

Some of these are more common in ALL in children than in adults.

Too many or too few chromosomes

Normal cells have 46 chromosomes (23 pairs of 2). In some people, the ALL cells have too many or too few chromosomes, without having other obvious chromosome changes. This can lead to too many or too few copies of certain genes that affect cell growth:

• In hyperdiploidy, the ALL cells have more than 50 chromosomes.
• In hypodiploidy, the ALL cells have fewer than 44 chromosomes.

Other chromosome changes

Other chromosome changes are also sometimes found in ALL cells, although they are less common. These include:

• Deletions: Loss of part of a chromosome
• Inversions: Rearrangement of the DNA within part of a chromosome
• Additions (duplications): An extra copy of part or all of a certain chromosome. (Having 3 full copies of a chromosome is known as trisomy.)

How chromosome and gene changes affect cell growth

Any type of chromosome change might affect genes that help control a cell’s growth. Sometimes, these types of genes are changed (mutated) without the whole chromosome being affected.

• Some of these changes might result in bone marrow cells becoming leukemia cells.
• Other changes might happen after leukemia has already formed, and these could affect how quickly the leukemia cells grow or how well they respond to certain treatments.

There are different subtypes of ALL, and even within a subtype, not all cases of ALL have the same gene or chromosome changes. Some changes are more common than others, and some seem to have more of an effect on a person’s prognosis (outlook) than others.

For more on some of the gene and chromosome changes that might be seen in ALL cells, see Acute Lymphocytic Leukemia (ALL) Subtypes and Prognostic Factors.

Are ALL gene changes inherited from a parent?

Gene changes can either be inherited from a parent or acquired during a person’s life. Some people with certain types of cancer have inherited gene mutations from a parent that increase their risk for the disease.

• Usually, gene mutations related to ALL are acquired during a person’s lifetime, not inherited from a parent.
• Inherited gene mutations are not a common cause of ALL (although they are a factor in some genetic syndromes that might increase a person’s risk for ALL).

How are these gene changes acquired?

Sometimes, gene changes related to ALL might happen because of outside causes like exposure to radiation or cancer-causing chemicals. But in most cases, the reason they happen isn't clear.

Many of these gene changes are probably just random events that sometimes happen inside a cell, without an outside cause. These changes can build up in our cells as we age, which might help explain why ALL in adults is more common as people get older.