Atypical chronic myeloid leukemia (aCML) is a rare, aggressive subtype of CML. Stem cell transplants are a potentially curative treatment, but people ineligible for a transplant may still benefit from chemotherapy.

Atypical CML is a rare type of blood and bone marrow cancer. It’s part of a group of blood and bone marrow conditions called myelodysplastic/myeloproliferative (MDS/MPN) neoplasms. It’s also known as BCR-ABL negative CML or Philadelphia chromosome (PH1) negative CML.

In aCML, bone marrow cells multiply excessively and produce abnormal, immature white blood cells called blasts.

Though it shares many features with typical CML, the types of abnormal cells present in aCML differ.

Atypical CML tends to be more aggressive than CML and is more challenging to diagnose and treat. For these reasons, it tends to have a less favorable outlook. Treatment involves medications to manage blood cell levels and, if you’re eligible, a stem cell transplant.

Your cells contain 23 pairs of chromosomes, which are made of DNA. Usually, a person with CML has a specific gene mutation where chromosomes 9 and 22 break and exchange pieces of DNA. This is called the BCR-ABL1 translocation.

However, people with aCML don’t have the BCR-ABL1 fusion gene, also called the Philadelphia chromosome.

Although CML is typically slow-growing, aCML tends to be more aggressive. It can also progress to an acute form of leukemia.

How rare is aCML?

Only 1% to 2% of people with CML have aCML. According to a 2023 study, just 103 people in the United States received a diagnosis of aCML between 2016 and 2020. The condition is more common in males and people over 65 years of age.

With aCML, your bone marrow can’t produce enough healthy blood cells. The lack of healthy blood cells results in low red blood cells (anemia) and low platelets (thrombocytopenia). This can cause typical CML symptoms, such as:

  • bruising
  • bleeding
  • fatigue
  • weakness
  • lightheadedness
  • infections
  • shortness of breath
  • pale skin, gums, or nails
  • headaches
  • unexplained weight loss

The World Health Organization (WHO) updated its criteria for diagnosing aCML in 2016. However, diagnosis can still be challenging due to the overlap of characteristics between CML and other MDS and MPN neoplasms.

Doctors diagnose aCML with a physical exam, blood sample, and bone marrow biopsy. You may receive a diagnosis after blood work for a regular checkup or if you’re having symptoms of CML.

A doctor may use diagnostic tests such as:

To diagnose aCML, a doctor will examine your blood cells and use tests to determine the levels of certain white blood cells, like basophils, granulocytes, monocytes, and leukocytes.

Current WHO criteria for diagnosing aCML include:

  • absence of Philadelphia chromosome, BCR/ABL fusion gene, and other genetic rearrangements (PDGFRA, PDGFRB, FGFR1, or PCM1-JAK2)
  • basophils less than 2%
  • few monocytes (less than 10% of leukocytes)
  • leukocytosis
  • more than 20% blasts in the blood and bone marrow
  • presence of immature circulating myeloid precursors (greater than or equal to 10% leukocytes)
  • dysgranulopoiesis, a condition that affects the production of granulocytes
  • hypercellular bone marrow, which is when the bone marrow has an excess of cells

Currently, there’s no standard treatment for managing aCML.

Treatment may include:

A stem cell transplant has the potential to cure the condition, but this option is only available to younger people due to the risks.

This differs from CML, where doctors typically first use targeted therapies that block the protein made by the BCR-ABL gene.

More research is needed to understand the molecular biology of aCML so that scientists can determine whether targeted therapies, like JAK inhibitors, are effective options. Your doctor may also recommend participating in a clinical trial.

Since aCML is rare, scientists lack large clinical trials to assess new treatment options.

Atypical CML tends to be more aggressive than CML and has a less favorable outlook. In a 2017 study of 25 people with aCML, the median overall survival was 10.8 months. Some research also suggests that aCML can develop into acute myeloid leukemia.

Stem cell transplants are the only potential cure for aCML, but they’re only an option for younger people. In one study, 87% of people receiving a stem cell transplant for aCML entered complete remission. However, after 5 years, 40% experienced a relapse.

Scientists aren’t exactly sure about what causes aCML, but they are aware of a few risk factors. These include:

  • age, as it’s more common in those older than 65 years of age
  • sex, as it’s more common in males than females
  • race, as it may be more common in white people

CML doesn’t run in families.

Atypical CML is a rare and aggressive type of cancer that affects regular blood cell production in the bone marrow.

Diagnosing and treating aCML can often be challenging, but new insights into the molecular biology of blood cancers have improved our understanding of aCML.

Larger studies are needed to help doctors understand how to manage the condition and improve the outlook.