B-lymphoblastic leukemia (B-ALL)

by David Li MD
August 20, 2025

B-lymphoblastic leukemia, also called B-cell acute lymphoblastic leukemia (B-ALL), is a type of blood cancer that starts in the bone marrow (the soft inner part of bones where blood cells are made). In this disease, the bone marrow produces large numbers of immature white blood cells called lymphoblasts.

These lymphoblasts come from a type of white blood cell called a B cell. Healthy B cells normally help the body fight infection. In B-ALL, however, the abnormal lymphoblasts do not mature properly or function like normal B cells. Instead, they multiply rapidly, crowding out healthy red blood cells, platelets, and other white blood cells. This leads to the symptoms and complications of leukemia.

What are the symptoms of B-lymphoblastic leukemia?

The symptoms of B-ALL happen because the bone marrow cannot make enough healthy blood cells. As a result, patients may experience:

  • Anemia (a shortage of red blood cells), which can cause fatigue, weakness, and shortness of breath.

  • Frequent infections (a shortage of normal w makes it harder to fight germs).

  • Easy bruising or bleeding (a shortage of platelets makes it harder to form blood clots).

  • Bone or joint pain.

  • Swollen lymph nodes.

  • Fever, night sweats, or unexplained weight loss.

What causes B-lymphoblastic leukemia?

The exact cause of B-ALL is not known. Most cases are thought to result from genetic changes that occur in bone marrow cells over time.

Some factors that increase the risk include:

  • Genetic conditions such as Down syndrome.

  • Radiation exposure (including previous cancer treatments with radiation).

  • Inherited variations in certain genes such as GATA3, ARID5B, IKZF1, CEBPE, and CDKN2A/B. These changes affect how blood cells grow and divide.

It is important to know that in most patients, B-ALL does not have a clear cause and is not something that could have been prevented.

What is the difference between B-lymphoblastic leukemia and B-lymphoblastic lymphoma?

B-lymphoblastic leukemia (B-ALL) and B-lymphoblastic lymphoma (B-LBL) are very similar diseases made up of the same type of cancer cell. The difference is where the cancer is found.

  • B-ALL is diagnosed when cancer cells are present in the bone marrow and blood.

  • B-LBL is diagnosed when the cancer cells are mainly found outside the bone marrow or blood, such as in the lymph nodes, liver, spleen, central nervous system, or skin.

Because of this overlap, the two conditions are often described together as B-ALL/LBL.

How is the diagnosis made?

Doctors usually begin investigating when a blood test shows an abnormal number of lymphocytes or blasts. To make a definite diagnosis, a bone marrow biopsy is performed. In this procedure, a small sample of bone marrow is removed and examined under the microscope by a pathologist.

Additional tests may also be performed, such as flow cytometry (to identify the types of proteins made by the cancer cells), immunohistochemistry, and genetic tests to look for DNA changes in the leukemia cells. These tests help confirm the diagnosis and classify the leukemia into subtypes.

What does B-lymphoblastic leukemia look like under the microscope?

When examined under the microscope, B-ALL typically shows the following features:

  • The bone marrow is usually packed with lymphoblasts that replace normal blood-producing cells.

  • Lymphoblasts are larger than normal lymphocytes. They have a large nucleus (the cell’s control center) that takes up most of the cell. The chromatin (genetic material in the nucleus) is fine and evenly spread, and small round structures called nucleoli may be seen inside the nucleus.

  • The cytoplasm (the part of the cell outside the nucleus) is thin and pale.

  • In blood smears, lymphoblasts may also be visible, often in very high numbers.

Because the blasts do not mature, very few normal B cells are present.

What other tests may be performed?

Flow cytometry and immunohistochemistry

These tests look at the proteins made by the cancer cells. In B-ALL, the lymphoblasts usually produce B cell markers such as CD19, CD22, and CD79a, along with other markers like CD10, PAX5, and TdT. Identifying these markers confirms that the blasts are immature B cells.

Genetic tests

Pathologists also perform tests such as FISH (fluorescence in situ hybridization), PCR (polymerase chain reaction), and next-generation sequencing (NGS) to look for genetic changes in the leukemia cells. These tests help divide B-ALL into subtypes.

Some subtypes are linked to a better prognosis, while others are more aggressive and may require more intensive treatment.

For example:

  • ETV6::RUNX1 fusion and high hyperdiploidy are associated with better outcomes.

  • KMT2A rearrangements and BCR::ABL1 fusion (Philadelphia chromosome) are linked to worse outcomes.

  • iAMP21 is associated with a higher chance of relapse and requires stronger therapy.

Minimal residual disease (MRD)

After treatment, very sensitive tests such as flow cytometry, PCR, or NGS are used to detect small numbers of cancer cells that may remain. This is called minimal residual disease (MRD). MRD testing is an important way to monitor treatment response and predict the risk of relapse.

Is B-lymphoblastic leukemia staged like other cancers?

Unlike solid tumours, acute leukemias are not staged using size or spread. Instead, prognosis depends on other factors, including:

  • Patient age (children generally do better than adults).

  • White blood cell count at diagnosis.

  • Genetic abnormalities in the leukemia cells.

  • Involvement of other organs such as the brain, spinal cord, or testes.

  • Response to therapy and MRD status after treatment.

Most children with B-ALL can achieve remission with treatment, while outcomes for adults are less favorable.

What happens after the diagnosis?

Patients with B-ALL are followed closely by a team of doctors, including hematologists and oncologists. Tests such as blood counts, bone marrow biopsies, and MRD testing are used to monitor how well the leukemia is responding to treatment. The results help guide decisions about whether more therapy is needed.

Questions to ask your doctor

If you have been diagnosed with B-lymphoblastic leukemia, you may wish to ask your doctor:

  • What subtype of B-ALL do I have, and what does it mean for my prognosis?

  • Were any genetic changes found in the cancer cells?

  • What tests will be used to monitor my disease during and after treatment?

  • How will minimal residual disease (MRD) testing be used in my care?

  • What are the treatment options available, and how do they differ for children and adults?

  • What symptoms or side effects should I expect during treatment?

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