Juvenile Myelomonocytic Leukemia (JMML)

July 23, 2025

This page was reviewed under our medical and editorial policy by Nicole Karras, M.D., associate clinical professor, Department of Pediatrics, City of Hope^® Cancer Center Duarte. 

Juvenile myelomonocytic leukemia (JMML) is a rare form of ​​childhood leukemia (​​blood cancer) that’s more common in males. This cancer type impacts 1 or 2 people for every 1 million people in the United States each year, making it very uncommon.

What Is JMML?

Juvenile myelomonocytic leukemia is also known as juvenile chronic myeloid leukemia, CMML of childhood, chronic and subacute myelomonocytic leukemia and infantile monosomy 7 syndrome.

JMML develops when the bone marrow produces too many abnormal monocytes — white blood cells that partner with other immune system cells and help fight off infections. The excess monocytes force out healthy white blood cells, red blood cells and platelets. As a result, patients with JMML can’t fight infections well. They may also become anemic or experience easy bleeding or bruising.

Overproduction of blood cells is called a ​​myeloproliferative disorder. When the blood cells produced are abnormal and not fully developed, a myelodysplastic disorder occurs. In cases of juvenile myelomonocytic leukemia, the two disorders often overlap. That’s why the World Health Organization (WHO) has categorized juvenile myelomonocytic leukemia as a myelodysplastic/myeloproliferative neoplasm.

Juvenile Myelomonocytic Leukemia Symptoms

JMML symptoms may develop over a span of weeks or months. The signs and symptoms may include:

• Difficulty breathing and/or dry cough
• Enlarged lymph nodes
• Abdominal pain and loss of appetite caused by enlarged kidney, liver and/or spleen
• Bone and joint pain
• Fatigue and pale skin due to anemia (low level of red blood cells)
• Easy bruising and bleeding due to thrombocytopenia (low level of platelets)
• Frequent infections due to neutropenia (low level of neutrophils, a type of white blood cell)
• Bone and joint pain

In some cases, skin changes may occur, such as:

• Raised red bumps in the skin (maculopapular rash)
• Bluish or greenish discolorations (chloromas)
• Smooth coffee-colored skin lesions (café au lait spots)

What Causes JMML?

While the specific cause of most childhood leukemia cases is unknown, researchers have found that nearly all JMML patients have changes (mutations) in the RAS genes or a chromosomal abnormality.

These changes cause white blood cells, or monocytes, to grow uncontrollably.

Risk Factors

JMML is more common in males, and the average age at diagnosis is just under 2 years. This condition may be associated with specific genetic mutations or abnormal chromosome changes. In fact, more than 95% of patients with JMML have a genetic mutation in the RAS pathway, including NRAS, KRAS, RRAS, RRAS2, PTPN11, NF1, CBL and SH2B3. The following changes and related syndromes may increase the risk of developing JMML.

RAS family gene mutations: These mutations include NRAS, KRAS, RRAS and RRAS2 and affect about 25% to 30% of patients.

NF1 gene mutation: Around 15% of JMML patients have this mutation and 10% to 15% of them are also diagnosed with neurofibromatosis 1, a condition that causes tumors in the brain, spinal cord or nerves.

PTPN11 gene mutation: About 35% of JMML patients have this mutation, which is related to Noonan syndrome, a rare genetic condition that’s present from birth and causes a short stature, short neck and heart defects.

CBL gene mutation: Occurring in approximately 15% of JMML patients, this mutation may lead to a disorder featuring poor growth, developmental delay and a predisposition to JMML.

Secondary mutations: Approximately 25% to 35% of JMML patients have secondary gene mutations, including SETBP1, SH2B3, DNMT3A, ASXL1, EZH2, GATA2 and RUNX1, which may occur inside or outside the RAS pathway.

Chromosome 7 abnormalities: Monosomy 7 and other chromosome 7 abnormalities occur in about 25% to 30% of JMML patients.

Diagnosis and Testing

To diagnose juvenile myelomonocytic leukemia, the care team may first rule out other similar diseases such as chronic myelomonocytic leukemia and ​chronic myeloid leukemia, particularly if a child is older than 6 years.

These diagnostic tests include:

• ​Blood tests to measure blood cell levels, organ function and cancer biomarkers ​​
• Bone marrow aspiration and biopsy, which involves removing a sample of bone marrow cells for examination under a microscope
• Cytogenetic (chromosomal) and molecular (gene mutation) tests that look for abnormalities in the cancer cells

Because a RAS pathway mutation is found in more than 95% of JMML patients, next-generation sequencing is now standard of care — meaning all patients suspected of having JMML should undergo genetic analysis of their genes, comparing their tumor cells to their normal cells.

Treatment

With juvenile myelomonocytic leukemia, speed to specialized care matters. Without treatment, the disease progresses rapidly.

There are two common treatments for JMML: stem cell transplantation and drug therapy.

Pediatric Allogeneic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (HSCT), which involves using healthy stem cells from a donor, may be recommended for patients with JMML. Around half of the children who are treated with a ​pediatric stem cell transplant procedure for JMML are still free of leukemia after several years. Although relapse may occur, often within the first year, patients may be cured with a second stem cell transplant.

Drug Therapy

While ​​chemotherapy isn’t used to cure JMML, it’s sometimes used to clean the bone marrow and prepare the body to receive stem cells. These powerful drugs help manage the disease during the one-to-two-month lead-up period before a stem cell transplant.

The U.S. Food and Drug Administration has approved the chemotherapy drug azacitidine (Vidaza) for JMML patients aged 1 month and older.

Clinical Trials

​Clinical trials that explore newer drug therapies may be a good option for certain juvenile myelomonocytic leukemia patients who may not be able to get a stem cell transplant.

Who Treats JMML?

It’s important that patients with JMML receive multidisciplinary care from experts who specialize in treating ​​childhood cancer, including:

• Pediatric medical oncologists and hematologists, who specialize in diagnosing and treating children, teens and young adults with JMML, other ​​types of blood cancer or other blood disorders
• Pediatric surgeons, who perform complex surgical techniques to remove tumors from the body
• Pediatric radiation oncologists, who use high-energy beams of radiation to destroy cancerous tissue
• Pathologists, who examine tissue samples to help diagnose cancer and other diseases
• Pediatricians, who focus on preventing, diagnosing and treating childhood diseases and injuries
• Pediatric oncology nurses, who provide specialized care for children during their hospital treatments and stays
• Supportive care providers, who offer an array of physical, psychological and emotional support to patients and their loved ones

Complications and Side Effects

Like most treatments, chemotherapy and stem cell transplants may cause complications and side effects. For most patients, they are temporary, but in some cases they may be severe.

Most side effects are tied to chemotherapy used during the preparation period before a stem cell transplantation. While destroying cancer cells, these drugs often damage normal cells in the process, including those in the lining of the mouth, throat, stomach and intestines.

Common side effects of JMML treatment include:

• Nausea and vomiting
• Diarrhea
• Infections
• Mouth sores
• Hair loss
• Slow growth rate
• Low levels of red blood cells, white blood cells and platelets in the blood
• Congestive heart failure

​Graft-versus-host disease, or GVHD, is a potentially serious complication of allogeneic stem cell transplantation, where donor stem cells (graft) attack healthy cells in the patient (host).

Prognosis and Survival Rate

Although it’s aggressive and difficult to treat, juvenile myelomonocytic leukemia is cured with allogeneic hematopoietic stem cell transplantation in about 50% of cases. For patients with aggressive JMML who don’t receive a transplant, the median survival averages less than two years.

Outcomes for patients vary. Typically, less favorable outcomes are seen if the patient:

• Is older than 2 years
• Has elevated hemoglobin F levels
• Has low platelet counts at the time of diagnosis
• Has more than one gene mutation in JMML cells at diagnosis

In rare cases, JMML spontaneously improves without treatment.