Chronic Myelomonocytic Leukemia (CMML): Understanding Your Pathology Report

Section Editor: David Li MD
July 4, 2026

Chronic myelomonocytic leukemia (CMML) is a type of blood and bone marrow cancer in which the body makes too many monocytes, a kind of white blood cell that normally helps fight infection. It belongs to a group of diseases called myelodysplastic/myeloproliferative neoplasms, which means it shares features of both conditions. As in myelodysplastic syndromes, the blood cells in CMML often look abnormal and do not function properly, and, like in myeloproliferative neoplasms, the bone marrow tends to produce too many cells. The result is a persistent increase in monocytes in the blood, often along with low levels of other healthy blood cells.

This article will help you understand the findings in your pathology report for chronic myelomonocytic leukemia, what each term means, and why it matters for your care.

What are the symptoms of chronic myelomonocytic leukemia?

Many people with chronic myelomonocytic leukemia (CMML) have no symptoms at first and are diagnosed after a routine blood test shows a high monocyte count. When symptoms do develop, they are often related to low levels of healthy blood cells or to the buildup of abnormal cells in organs. Common symptoms include:

Fatigue and weakness — Caused by anemia (a low red blood cell count).
Frequent or severe infections — Because the body does not have enough normal, healthy white blood cells.
Easy bruising or bleeding — From a low platelet count.
An enlarged spleen or liver — Which can cause discomfort or fullness in the abdomen, more often in the proliferative type described below.
General symptoms — Such as fever, night sweats, and weight loss.

How common is chronic myelomonocytic leukemia?

Chronic myelomonocytic leukemia (CMML) is uncommon. It is a disease of older adults, with most people diagnosed after the age of 70, and it affects men more often than women. It is rare in younger adults and children.

What causes chronic myelomonocytic leukemia?

Chronic myelomonocytic leukemia (CMML) is caused by acquired genetic mutations (changes in the DNA) that develop in a blood-forming stem cell in the bone marrow during a person’s life. These changes are not inherited and are not passed on to children. As a person ages, blood-forming cells can gradually accumulate mutations, and in some people these changes eventually lead to CMML. Because the abnormal cells all come from a single altered stem cell, CMML is described as a clonal disorder, meaning the cells are copies of one another.

What genetic changes are involved in chronic myelomonocytic leukemia?

More than 90% of people with chronic myelomonocytic leukemia (CMML) have one or more gene mutations in the abnormal cells, and finding them helps confirm that the disease is a true clonal cancer rather than a temporary reaction. The most common changes involve the genes:

TET2 — Found in about 60% of cases.
SRSF2 — Found in about half of cases.
ASXL1 — Found in about 40% of cases and linked with a less favorable outlook.
RAS pathway genes (such as NRAS and KRAS) — More common in the proliferative type and associated with faster-growing disease.

These changes are usually detected using next-generation sequencing, a test that examines many genes at once. Your report will list any mutations that were found, and some of them, particularly ASXL1, help predict how the disease is likely to behave.

How is the diagnosis made?

The diagnosis of chronic myelomonocytic leukemia (CMML) is based on blood tests, a bone marrow examination, and genetic testing, together with the exclusion of other causes of a high monocyte count. The key blood finding is a persistent increase in monocytes, defined as a monocyte count of at least 0.5 x 10⁹/L that accounts for at least 10% of white blood cells, lasting for three months or more. A blood smear, a thin layer of blood examined under the microscope, is used to confirm the increase in monocytes and to look for abnormal or immature cells.

A bone marrow biopsy and aspiration are performed so that a pathologist can examine the bone marrow. In CMML, the marrow is usually crowded with cells, shows an increased number of monocytes and their precursors, and contains cells that look abnormal, a feature called dysplasia. The pathologist also counts the proportion of immature cells called blasts; in CMML, blasts make up less than 20% of cells, because 20% or more would indicate acute leukemia. Flow cytometry can support the diagnosis by showing a characteristic shift in the types of monocytes present, helping distinguish CMML from a harmless rise in monocytes.

Because a high monocyte count can also occur as a normal response to infection, inflammation, or other illnesses, these reactive causes must be ruled out. Genetic testing helps by confirming that the cells are clonal. Testing is also done to make sure the BCR::ABL1 fusion gene, which is found in chronic myeloid leukemia, is not present, because that condition can look similar but is treated differently.

What are the types of chronic myelomonocytic leukemia?

Doctors describe chronic myelomonocytic leukemia (CMML) in two ways that help predict how it will behave and guide treatment. The first is based on the total white blood cell count:

Myelodysplastic CMML (MD-CMML) — The white blood cell count is lower (less than 13 x 10⁹/L). This type behaves more like a myelodysplastic syndrome, with low blood counts as the main problem.
Myeloproliferative CMML (MP-CMML) — The white blood cell count is higher (13 x 10⁹/L or more). This type behaves more like a myeloproliferative neoplasm, often with an enlarged spleen, and is more often associated with RAS pathway mutations.

The second is based on the number of blasts, which reflects how advanced the disease is:

CMML-1 — Fewer blasts (less than 5% in the blood and less than 10% in the bone marrow).
CMML-2 — More blasts (5 to 19% in the blood or 10 to 19% in the bone marrow, or when structures called Auer rods are present). This type is more advanced and closer to acute leukemia.

What is the prognosis for chronic myelomonocytic leukemia?

The outlook for chronic myelomonocytic leukemia (CMML) varies widely. Some people have stable disease for years, while others progress more quickly, and about 15 to 20% eventually develop acute myeloid leukemia. To estimate risk and guide treatment, doctors use scoring systems designed specifically for CMML, such as the CMML-specific Prognostic Scoring System (CPSS) and its molecular version, which combine the number of blasts, the white blood cell count, the degree of low blood counts, the need for transfusions, chromosome changes, and gene mutations. Certain features, such as a higher blast count, a higher white blood cell count, more severe anemia or low platelet counts, an ASXL1 mutation, and certain chromosomal changes, are associated with higher-risk disease. Your prognosis depends on your own combination of these factors, which your care team can explain in the context of your specific report.

What happens after a diagnosis of chronic myelomonocytic leukemia?

After chronic myelomonocytic leukemia (CMML) is diagnosed, the risk category helps guide treatment, which is different for lower-risk and higher-risk disease. The pathology and genetic findings help shape several decisions:

Observation and supportive care — People with lower-risk disease and few or no symptoms may be monitored closely, with supportive treatments such as blood transfusions or medicines that stimulate red blood cell production to manage anemia.
Hydroxyurea — A medicine used to lower very high white blood cell counts and to shrink an enlarged spleen, particularly in the proliferative type.
Hypomethylating agents — Drugs such as azacitidine and decitabine can improve blood counts and are commonly used for higher-risk disease.
Stem cell (bone marrow) transplant — An allogeneic transplant, using blood-forming cells from a donor, is the only treatment that can cure CMML and is generally considered for higher-risk patients who are well enough.

Care is provided by a hematology team, and regular blood tests and follow-up help monitor the disease and detect any progression. Clinical trials of newer treatments may also be an option to discuss. Decisions about treatment are made by the care team together with the patient, based on the specific findings in the report.

Questions to ask your doctor

Is my disease the myelodysplastic type (MD-CMML) or the myeloproliferative type (MP-CMML)?
Am I in the CMML-1 or CMML-2 category based on my blast count?
What gene mutations were found, and do any of them affect my outlook?
Was I tested for the BCR::ABL1 fusion gene to rule out chronic myeloid leukemia?
What is my risk category based on CMML scoring systems?
Am I at risk of progressing to acute myeloid leukemia, and what signs should I watch for?
Do I need treatment now, or is careful monitoring reasonable for me?
If I need treatment, which option is best for my situation?
Should I be evaluated for a stem cell transplant?
How will my anemia, infections, or bleeding risk be managed?
Are there clinical trials that I should consider?