Juvenile Myelomonocytic Leukemia (JMML)

At first, a physician will take the patient’s medical history and will perform a physical exam. During the physical exam, the doctor will check general signs of health, including signs of disease, such as lumps or anything else that seems unusual. The eyes, mouth, skin, and ears will be looked at carefully, and a nervous system exam may be done. The doctor may feel the patient’s abdomen for signs of an enlarged spleen or liver.

Complete blood count

Doctors will order a blood test called a complete blood count. A sample of blood is drawn and checked for the:

• Number of red blood cells and platelets
• Number and type of white blood cells
• Amount of hemoglobin in the red blood cells
• Portion of the blood sample made up of red blood cells. 

Abnormal numbers of monocytes (a type of white blood cell) is a feature of JMML.

Blood chemistry studies

A blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease. In JMML, one of the examples is hypergammaglobulinemia (a higher than normal amount of gammaglobulin-an infection-fighting protein.)

Bone marrow tests, like a bone marrow aspiration and biopsy, will confirm a diagnosis of cancer and pinpoint the type of cancer. Most children are asleep (sedated) during the procedure. If awake during the procedure, patients are given appropriate pain medicine.

Bone marrow aspiration: Doctors will obtain a bone marrow sample by inserting a thin, hollow needle into the hipbone. A pathologist will view the bone marrow under a microscope to look for signs of cancer.

Bone marrow biopsy: Doctors will remove a small piece of bone tissue to determine how much the cancer has spread in the bone marrow. The biopsy is typically performed right before or after the aspiration.

How is a bone marrow aspiration / biopsy performed?

• Patients will lie on their side on the bed, or, less commonly, sit up with legs bent and crossed at the ankles. 
• The doctor or nurse practitioner will feel the patient’s lower back to find the right spot for the test. 
• Next, the health care provider will put on gloves and clean the patient’s back with a germ-killing soap. Then, the health care provider might place plastic towels over the back, leaving only a small area of skin showing. 
• If the health care provider is going to be awake during the aspirate or biopsy, numbing cream will be placed on the spot where the bone marrow aspirate or biopsy will be taken about one hour before the procedure. Liquid numbing medicine might be injected at the procedure site. 
• The health care provider will push a needle through the skin into the bone marrow. If both an aspiration and biopsy are done, a separate needle will be used for each procedure.
• The health care provider will take out the needle, clean the spot with alcohol, and put on a bandage.

Immunophenotyping is used to diagnose specific types of leukemia by comparing the cancer cells to normal cells of the immune system.

Immunohistochemistry and flow cytometry are the laboratory tests.

• Immunohistochemistry is a test that uses antibodies to show specific proteins in a sample of tissue. The complexes of proteins and antibodies are stained brown or red and can be seen under a microscope.
• In flow cytometry, cells are stained with a light-sensitive dye, placed in a fluid, and passed in a stream before a laser or other type of light. The test measures the number of cells, the percentage of live cells, and certain characteristics of cells, such as size, shape, and the presence of tumor markers on the cell surface.

Cytogenetic analysis involves laboratory tests in which pathologists look for certain changes in the chromosomes. There are several cytogenetic changes in JMML. The most common are abnormalities of chromosome 7 and 8. Loss of chromosome 7 (monosomy 7) occurs in about 30% of the children with JMML.

One such test is FISH (fluorescence in situ hybridization). This test looks at genes or chromosomes in cells and tissues. Pieces of DNA that contain a fluorescent dye are made in the laboratory and added to cells or tissues on a glass slide. When these pieces of DNA attach to certain genes or areas of chromosomes on the slide, they light up.

Molecular and genetic testing is the most important component of the diagnosis of JMML. The doctor may recommend running laboratory tests to identify specific genes, proteins, and other factors involved in leukemia. This examination is important because cancer is caused by mistakes (mutations) in the cell’s genes. The vast majority of children with JMML have somatic and/or germline mutations of genes involved in the RAS/MAPK signaling pathway. A signaling pathway is a group of molecules in a cell that works together to control one or more cell functions, such as cell division or cell death. After the first molecule in a pathway receives a signal, it activates another molecule. This process is repeated until the last molecule is activated and the cell function is carried out. Abnormal activation of signaling pathways can lead to cancer, and drugs are being developed to block these pathways. These drugs may help block cancer cell growth and kill cancer cells. Mutations in NF1, PTPN11, KRAS, NRAS, or CBL are found in about 90 percent of patients with JMML.