Chronic myelomonocytic leukaemia (CMML) is a rare blood cancer that develops when the bone marrow begins producing too many abnormal white blood cells called monocytes, gradually disrupting the body’s ability to make other essential blood cells needed for health.

Understanding Chronic Myelomonocytic Leukaemia

Chronic myelomonocytic leukaemia is an uncommon type of blood cancer that affects how your bone marrow produces blood cells. The bone marrow is the spongy tissue inside your bones that acts like a factory for making all the different blood cells your body needs to stay healthy. When someone has CMML, this factory starts making too many of a specific type of white blood cell known as monocytes, which normally help your immune system fight infections.^[1]

What makes this condition particularly challenging is that these monocytes are not only overproduced but also abnormal, meaning they don’t work properly. As these faulty cells accumulate in your bone marrow and bloodstream, they crowd out the space and resources needed to make other vital blood cells like red blood cells that carry oxygen, platelets that help blood clot, and other types of white blood cells that protect against disease.^[4]

Medical experts classify CMML as both a myelodysplastic syndrome and a myeloproliferative neoplasm. This dual classification reflects that CMML shares features of two different types of blood disorders. The myelodysplastic part means the bone marrow produces abnormal, immature cells that don’t function correctly. The myeloproliferative part means the bone marrow makes too many cells of a particular type. CMML sits at the intersection of these two problems.^[1]

The disease typically progresses slowly, which is why it’s called “chronic.” However, CMML can range from slow-growing to more aggressive forms depending on various factors. Healthcare providers use classification systems to determine how serious each case is, based on the number of immature blast cells found in blood and bone marrow samples.^[5]

How Common is CMML?

Chronic myelomonocytic leukaemia is quite rare compared to many other cancers. In the United Kingdom, approximately 650 people receive a CMML diagnosis each year.^[6] Data from the United States shows an incidence rate of about 0.4 cases per 100,000 people annually, though exact numbers can be difficult to determine because the condition is so uncommon.^[10]

This disease predominantly affects older adults. The median age when people are diagnosed with CMML falls between 70 and 75 years old. A median age means that half of all people diagnosed are younger than this range, and half are older. Some younger individuals do develop CMML, and doctors sometimes refer to people diagnosed before age 65 as “young CMML” patients, but these cases are relatively uncommon.^[10]

There is also a clear pattern regarding who develops CMML based on biological sex. Men are diagnosed with this condition about twice as often as women. The reasons for this gender difference are not fully understood, but it represents a consistent finding across different populations studied.^[6]

What Causes Chronic Myelomonocytic Leukaemia?

Scientists do not know exactly what triggers CMML to develop in most cases. The condition arises from genetic changes that occur in stem cells within the bone marrow during a person’s lifetime. These are not inherited mutations passed down from parents, nor can they be passed on to children. Instead, they happen spontaneously as cells age and divide over many years.^[6]

Researchers have identified several specific genes that commonly undergo changes in people with CMML. The most frequently mutated genes include TET2, which is altered in about 60% of cases, SRSF2 in approximately 50% of cases, ASXL1 in around 40% of cases, and genes in the RAS pathway in about 30% of cases. Most people diagnosed with CMML have mutations in more than one of these genes.^[10]

These genetic mutations appear to happen by chance in most cases. CMML often develops against a background of what doctors call clonal haematopoiesis, a condition where some blood cells begin to develop from a single mutated stem cell as part of the normal aging process. In some people, additional mutations then accumulate, eventually leading to CMML.^[10]

The genetic changes don’t happen all at once. Research suggests that TET2 and SRSF2 mutations are often early initiating events. Subsequently, when additional mutations in genes like ASXL1, RUNX1, or RAS pathway genes occur, the full picture of CMML emerges. Different combinations of these mutations can lead to different subtypes of the disease with varying characteristics and behaviors.^[10]

Risk Factors for Developing CMML

While the exact cause of CMML remains unknown, several factors can increase a person’s likelihood of developing this condition. The most significant risk factor is age. As people get older, their risk of developing CMML increases considerably. This is consistent with the median diagnosis age falling in the early to mid-70s, reflecting that this is primarily a disease of aging.^[1]

Being male is another risk factor, as men develop CMML approximately twice as often as women. The biological reasons behind this sex difference are not completely understood, but the pattern holds true across different populations and studies.^[5]

Previous cancer treatment represents an important but relatively uncommon risk factor. About one in ten people who develop CMML had received chemotherapy or radiation therapy for a different cancer in the past. When CMML develops under these circumstances, doctors call it therapy-related or treatment-related CMML. However, it’s crucial to understand that most people with CMML have never had previous cancer treatment.^[6]

Healthcare providers carefully consider the potential risk of future cancers when prescribing chemotherapy or radiation. They only recommend these treatments when the benefits of treating the current cancer clearly outweigh the risks of possible future complications. The absolute risk of developing treatment-related CMML remains quite low even among those who receive these therapies.^[1]

Recognizing the Symptoms of CMML

One of the challenging aspects of CMML is that it often doesn’t cause noticeable symptoms in its early stages. Many people first learn they have CMML when routine blood tests reveal abnormal results, even though they feel completely well. When symptoms do appear, they typically develop gradually over time rather than suddenly.^[1]

The most common symptom is persistent fatigue or weakness that doesn’t improve with rest. This occurs when the bone marrow fails to produce enough red blood cells, a condition called anaemia. Without sufficient red blood cells to carry oxygen throughout the body, people may also experience breathlessness, particularly during physical activity, or feel dizzy.^[4]

Some people with CMML develop frequent or persistent infections. This happens because even though the bone marrow produces many white blood cells, they are abnormal and cannot effectively fight off bacteria, viruses, or other pathogens. These infections may not respond to treatment as quickly as expected or may keep returning.^[1]

Excessive bleeding or easy bruising can occur when the condition reduces the number of platelets, the blood cells responsible for clotting. People might notice nosebleeds that are difficult to stop, bleeding gums when brushing teeth, or bruises appearing with minimal or no injury. Small red or purple spots on the skin called petechiae may also appear.^[6]

CMML can cause the spleen to enlarge, a condition known as splenomegaly. Because the spleen sits on the left side of the abdomen just beneath the ribs, an enlarged spleen may cause discomfort, pain, or a feeling of fullness in that area. Some people also experience an enlarged liver, which can cause similar sensations on the right side of the abdomen.^[1]

Additional symptoms that may develop include unexplained weight loss without trying, night sweats that soak through clothing or bedding, persistent low-grade fever without an obvious infection, and aching bones or joints. Some people also develop skin problems such as rashes or lumps under the skin where abnormal cells have accumulated.^[5]

Prevention: Is It Possible?

Unfortunately, there are no known ways to prevent CMML from developing. Because the genetic mutations that cause this condition occur spontaneously during a person’s lifetime and scientists don’t understand why they happen, there are no lifestyle changes, dietary measures, or screening tests currently available that can prevent CMML.^[6]

The one exception relates to treatment-related CMML. Healthcare providers already take great care when prescribing chemotherapy or radiation therapy, carefully weighing the benefits of treating the current cancer against the small risk of possibly developing a second cancer like CMML years later. These decisions are made thoughtfully, and patients should always discuss any concerns about treatment risks with their oncology team.^[1]

While CMML itself cannot be prevented, people who have been diagnosed can take steps to maintain their overall health and potentially reduce complications. Eating a balanced, nutritious diet helps support the body during treatment. Gentle exercise, approved by a doctor, can help maintain strength and energy levels when possible. Getting adequate rest when feeling tired is also important.^[6]

People with CMML should take extra precautions to avoid infections, as their immune systems may not work properly. This includes practicing good hand hygiene, avoiding crowds during cold and flu season when possible, staying up to date with recommended vaccinations, and promptly reporting any signs of infection to their healthcare team.^[18]

How CMML Affects the Body

Understanding what happens inside the body when someone has CMML helps explain why symptoms occur and how treatments work. The process begins in the bone marrow, where all blood cells are born. In a healthy person, stem cells in the bone marrow divide and mature into three main types of blood cells: red blood cells, white blood cells, and platelets. Each type has specific, crucial jobs.^[4]

Red blood cells contain a protein called haemoglobin that binds to oxygen in the lungs and carries it to tissues throughout the body. White blood cells include several subtypes that work together to identify and destroy bacteria, viruses, and other threats to health. Platelets are cell fragments that rush to sites of blood vessel injury and stick together to form clots, preventing excessive bleeding.^[4]

In CMML, genetic mutations cause stem cells to malfunction. Instead of producing balanced numbers of mature, functional blood cells, the mutated stem cells generate excessive quantities of monocytes, a specific type of white blood cell. Normally, monocytes circulate in the blood and move into tissues where they transform into macrophages, large cells that engulf and digest foreign particles and dead cells. They play an important role in both fighting infections and cleaning up cellular debris.^[4]

However, in CMML, the bone marrow produces far too many monocytes, and these cells are often abnormal. They may not mature properly, remaining as immature blast cells, or they may mature but fail to function correctly. These faulty monocytes accumulate in the bone marrow, taking up space and consuming resources that should support the production of other blood cells.^[5]

As abnormal monocytes crowd the bone marrow, production of red blood cells declines, leading to anaemia. The resulting shortage of oxygen-carrying capacity causes fatigue, weakness, and breathlessness. Production of healthy white blood cells also falls, weakening the immune system and increasing vulnerability to infections. Platelet production decreases as well, impairing the blood’s ability to clot and leading to easy bruising and bleeding.^[10]

The abnormal cells can also accumulate outside the bone marrow. Collections of these cells in the spleen and liver cause these organs to enlarge. Sometimes abnormal cells form deposits in the skin, appearing as rashes or raised lumps. In more advanced cases, blast cells may increase in the blood and bone marrow, signaling progression toward a more aggressive form of leukaemia.^[1]

Doctors classify CMML into subtypes based on laboratory findings that reflect what’s happening in the bone marrow. One classification separates cases into CMML-1 and CMML-2 based on the percentage of blast cells in the blood and bone marrow. CMML-2 has higher blast percentages and generally indicates more aggressive disease. Another classification distinguishes between dysplastic CMML, which primarily features low blood cell counts and related symptoms, and proliferative CMML, which involves higher white blood cell counts and often more constitutional symptoms like fever, weight loss, and night sweats.^[10]

The proliferative subtype tends to behave more aggressively, with higher rates of transformation to acute leukaemia. The specific genetic mutations present in each case also influence how the disease behaves. For example, cases with RAS pathway mutations often fall into the proliferative category and may be harder to treat, while cases with TET2 mutations but without ASXL1 mutations tend to respond better to certain therapies.^[10]