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Juvenile chronic myelomonocytic leukaemia – Basic Information

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Juvenile myelomonocytic leukaemia (JMML) is a very rare blood cancer that primarily affects young children, most commonly those under the age of two. This slowly developing disease occurs when certain types of white blood cells grow abnormally in the bone marrow, affecting the body’s ability to fight infections and produce healthy blood cells.

Epidemiology

Juvenile myelomonocytic leukaemia is an extremely rare condition, occurring much less frequently than other childhood blood cancers. The annual incidence is estimated at approximately one to two cases per one million people, making it about ten times less common than acute myeloid leukemia (a fast-growing blood cancer) in children.[1][2]

The disease shows distinct patterns in who it affects. More than half of all children diagnosed with JMML are under two years old, with the median age at presentation being approximately 1.8 years. This means that most children are very young when the disease is discovered. Children of any age can develop JMML, but it is exceptionally rare in older children and teenagers.[3][6]

JMML occurs more commonly in boys than in girls. The male-to-female ratio is approximately 2.5 to 1, meaning that for every girl diagnosed with this condition, about two to three boys receive the same diagnosis. The reasons for this gender difference are not understood.[3][6]

Causes

The exact cause of juvenile myelomonocytic leukaemia remains unknown, and researchers have not identified specific ways to prevent it. Parents should understand that this is not something caused by anything they did or did not do, and no one is to blame for a child developing this condition.[3]

JMML develops when genetic changes occur in stem cells within the bone marrow. Stem cells are early cells that have the potential to develop into all types of blood cells. These genetic changes cause the stem cells to malfunction, leading them to produce abnormal white blood cells, particularly monocytes and myelocytes (two specific types of white blood cells that normally help fight infections).[1][4]

Many children with JMML have mutations in genes that are part of what is called the RAS pathway. These include mutations in genes such as NRAS, KRAS, PTPN11, and others. These genetic changes affect how monocytes develop and function. Most of these mutations happen by chance during a child’s lifetime rather than being inherited from parents. In most cases, these genetic changes cannot be passed to any children the affected person might have in the future.[2][6]

In some children, the genetic mutations occur at the germline level, meaning they are present from birth. When this happens, it usually results in a transient or temporary form of the disease that may resolve on its own. However, when the mutations occur only in the blood cells and not in the germline (called somatic mutations), the disease tends to behave more aggressively.[2]

Risk Factors

While JMML can develop in any child, certain genetic conditions increase the risk of developing this disease. Children with neurofibromatosis type 1 (NF1), a genetic disorder that causes tumours to grow on nerves, have a higher likelihood of developing JMML. However, this connection is seen in only between 10 to 15 out of every 100 cases of JMML, meaning the vast majority of children with JMML do not have neurofibromatosis.[1][3]

Children with Noonan syndrome, another genetic condition that affects development in various parts of the body, also have an increased risk of developing JMML. Some children with Noonan syndrome may develop a JMML-like condition that is temporary and resolves without treatment.[1][6]

The disease can happen spontaneously by chance or can be associated with these genetic disorders. Most children who develop JMML have no known risk factors, and the disease appears without warning. There are no known environmental factors, lifestyle choices, or exposures during pregnancy that have been linked to causing JMML.[4]

Symptoms

Juvenile myelomonocytic leukaemia typically develops slowly over time, taking weeks to months for symptoms to become noticeable. At first, children may have very few symptoms, which can make early detection challenging. Some children are diagnosed after routine blood tests done for other reasons reveal abnormal results.[1][3]

As the disease progresses, children often develop anemia, which occurs when the body has too few red blood cells. Anemia happens because the abnormal cells crowd the bone marrow, preventing it from making the usual amount of red blood cells. Children with anemia may look pale, feel extremely tired or weak, need more naps than usual, and may become short of breath while playing or during other activities. Their heart may race as it tries to compensate for the low oxygen levels in the blood.[1][4]

When children don’t have enough platelets (small blood cells that help blood clot), they may bruise very easily, even from minor bumps. They may also experience nosebleeds or bleeding gums, and even minor cuts may bleed for a longer time than normal. Parents might notice unusual bruising appearing on their child’s body without any clear injury.[1][4]

Children with JMML frequently experience pain in their bones or joints. This pain can sometimes cause a child to limp or avoid certain activities. This symptom is often mistaken for normal growing pains, which can delay diagnosis. The pain results from the bone marrow being crowded with abnormal cells.[1][4]

Fever is a common symptom, present in approximately 54% of children at diagnosis. Children may also get many infections or find it more difficult to recover from common childhood illnesses. This happens because the white blood cells produced in JMML are immature and don’t work properly to fight germs, even though blood tests may show a high white blood cell count.[3][6]

Most children with JMML develop an enlarged liver and spleen, a condition called hepatosplenomegaly, which occurs in approximately 97% of cases. Parents may notice their child’s belly appears swollen or that their child has suddenly jumped a nappy or trouser size. The child may complain of pain or discomfort in the tummy area. This enlargement happens because abnormal white blood cells accumulate in these organs.[6][7]

Swollen lymph nodes, also called swollen glands, are found in approximately 76% of children at diagnosis. These may be noticeable in the neck, groin, or other areas of the body. Some children develop skin rashes, which occur in about 36% of cases. Other symptoms can include poor appetite, weight loss, being unusually irritable, taking longer to settle, general feelings of being unwell, and cough and wheezing.[3][6][7]

⚠️ Important
Many symptoms of JMML are similar to those of other common childhood illnesses, which can make diagnosis challenging. The disease develops fairly slowly, meaning symptoms might appear gradually over weeks or months. If your child has persistent or worsening symptoms, especially combinations such as ongoing fatigue with frequent infections or unexplained bruising, it’s important to consult with a doctor for proper evaluation.

In some cases, the abnormal cells can spread to other parts of the body. If JMML spreads to the brain, symptoms may include headaches, seizures, problems with balance, or vision problems. If it spreads to lymph nodes in the chest, children may experience breathing difficulties and chest pain.[1]

Prevention

Currently, there are no known methods to prevent juvenile myelomonocytic leukaemia. Because the exact causes of the disease are not fully understood and the genetic changes that lead to JMML occur spontaneously or in connection with other genetic conditions, there are no specific lifestyle changes, dietary modifications, or screening programmes that can prevent its development.[3]

For children with neurofibromatosis type 1 or Noonan syndrome, regular medical monitoring is important. While this doesn’t prevent JMML, it may help with earlier detection if the disease does develop. Doctors familiar with these conditions may monitor blood counts more closely in affected children.[1]

Pathophysiology

The World Health Organization classifies juvenile myelomonocytic leukaemia as a type of blood cancer that falls into a category called myelodysplastic/myeloproliferative neoplasms. This classification reflects that JMML has features of two different types of blood disorders. Although JMML has “leukaemia” in its name, it is not classified as a typical leukaemia but rather as an overlap disorder.[3][6]

A myeloproliferative disorder is a condition where the bone marrow makes too many blood cells. A myelodysplastic disorder is where the blood cells made are abnormal and not fully mature. JMML shows characteristics of both these problems. In reality, the two types of disorders often overlap, which is why JMML is placed in this special category.[3]

The bone marrow is a spongy material that fills the inside of bones. It normally contains early blood cells called stem cells, which develop into three different types of blood cells: red blood cells that carry oxygen, white blood cells that fight infections, and platelets that help blood clot. In a healthy child, stem cells in the bone marrow continuously divide to make new blood cells, keeping the numbers circulating in the blood within a normal range.[3]

In JMML, immature blood cells called blasts make too many monocytes and myelocytes. Monocytes are part of the immune system and normally help the body fight infection. However, in JMML, too many monocytes are produced, and they are not developed enough to work properly. These abnormal cells accumulate in the bone marrow and then enter the bloodstream, where they circulate around the body.[1][4]

The abnormal monocytes and myelocytes crowd the bone marrow, taking up space that should be occupied by healthy, developing blood cells. This crowding makes it difficult for the bone marrow to produce sufficient numbers of normal red blood cells, platelets, and other types of white blood cells. This is why children with JMML develop anemia, bleeding problems, and frequent infections.[3]

The abnormal white blood cells don’t function normally, meaning children with JMML don’t have the same protection against infection as healthy children, even though blood tests may show high numbers of white blood cells. The cells simply cannot do the job they are supposed to do. This leaves children vulnerable to various infections and makes it harder for them to recover from illnesses that healthy children would easily overcome.[3]

At the molecular level, JMML is associated with mutations in genes that are part of the RAS signaling pathway. These genetic changes result in myeloid precursor cells becoming excessively sensitive to granulocyte monocyte colony-stimulating factor (GM-CSF), a substance that normally helps regulate blood cell production. This abnormal sensitivity drives the overproduction of monocytes characteristic of the disease.[2]

Laboratory findings in JMML typically include high white blood cell counts, increased numbers of monocytes, elevated levels of hemoglobin F (a type of hemoglobin normally found in fetuses and newborns), and circulating immature cells called myeloid precursors. Importantly, the blast cells in the blood or bone marrow make up less than 20% of cells, and a specific genetic change called the BCR-ABL translocation is absent. These features help doctors distinguish JMML from other types of leukaemia.[2][6]

Ongoing Clinical Trials on Juvenile chronic myelomonocytic leukaemia

References

https://kidshealth.org/en/parents/jmml.html

https://pmc.ncbi.nlm.nih.gov/articles/PMC8010610/

https://www.cancerresearchuk.org/about-cancer/childrens-cancer/juvenile-myelomonocytic-leukaemia-jmml

https://www.chop.edu/conditions-diseases/juvenile-myelomonocytic-leukemia-jmml

https://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/childhood-blood-cancers/juvenile-myelomonocytic-leukaemia/

https://www.cancer.gov/types/leukemia/hp/child-aml-treatment-pdq/childhood-jmml-treatment-pdq

https://www.cancer.gov/types/leukemia/hp/child-aml-treatment-pdq/childhood-jmml-treatment-pdq

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FAQ

Is JMML the same as other types of childhood leukaemia?

No, JMML is different from other childhood leukaemias. Although it has “leukaemia” in its name, the World Health Organization classifies it as a myelodysplastic/myeloproliferative neoplasm, not as a typical leukaemia. It has features of both disorders where too many blood cells are made and where abnormal, immature blood cells are produced. It develops more slowly than acute leukaemias and primarily affects very young children.

Why does my child keep getting infections if their white blood cell count is high?

Although blood tests may show high numbers of white blood cells in children with JMML, these cells are immature and abnormal, meaning they cannot function properly. White blood cells normally fight infections, but in JMML they don’t work correctly. This leaves children vulnerable to infections and makes it harder for them to recover from common illnesses, even though there appear to be many white blood cells in the blood.

Can JMML be prevented or does it run in families?

There is no known way to prevent JMML. The genetic changes that cause it usually happen by chance during a child’s lifetime and are not inherited from parents. Most children with JMML have no family history of the disease. While children with certain genetic conditions like neurofibromatosis type 1 or Noonan syndrome have a higher risk, the vast majority of children with JMML do not have these conditions.

Why does my child’s tummy look swollen?

Most children with JMML develop an enlarged liver and spleen, a condition called hepatosplenomegaly. This happens because abnormal white blood cells accumulate in these organs, causing them to swell. Parents may notice their child’s belly appears larger or that their child has suddenly needed larger nappies or trousers. This occurs in approximately 97% of children with JMML.

How quickly does JMML develop?

JMML is considered a slowly developing or chronic blood cancer. Symptoms typically develop over weeks to months rather than appearing suddenly. At first, children may have very few symptoms, which can make early detection challenging. This slow development means that some children are diagnosed after blood tests done for other reasons reveal abnormalities.

🎯 Key takeaways

  • • JMML is an extremely rare blood cancer affecting mainly children under two years old, with only one to two cases per million people annually.
  • • The disease develops slowly over weeks to months, and early symptoms like tiredness and pale skin can be easily mistaken for common childhood illnesses.
  • • Boys are affected about 2.5 times more often than girls, though the reason for this difference is unknown.
  • • Most children with JMML develop enlarged liver and spleen, which parents may notice as a swollen belly or suddenly needing larger clothes.
  • • Children with genetic conditions like neurofibromatosis type 1 have a higher risk, but the vast majority of JMML cases occur in children with no known risk factors.
  • • The abnormal white blood cells in JMML don’t work properly, leaving children vulnerable to frequent infections even when blood counts appear high.
  • • There is no way to prevent JMML, and it is not caused by anything parents did or did not do.
  • • Some children with certain genetic mutations may develop a temporary form of the disease that resolves without treatment, unlike the typical aggressive form.

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