Diagnosing juvenile myelomonocytic leukemia (JMML) usually involves ruling out other similar diseases such as chronic myelomonocytic leukemia and chronic myeloid leukemia, especially if your child is older than 6 years. Doctors commonly use blood tests and bone marrow tests to diagnose JMML.
Bone marrow testing involves two steps usually done at the same time in a doctor's office or a hospital:
- A bone marrow aspiration to remove a liquid marrow sample
- A bone marrow biopsy to remove a small amount of bone filled with marrow
Lab Test to Confirm a Diagnosis
After the doctor takes samples of your child's blood and bone marrow, a hematopathologist confirms a diagnosis and looks for damage to chromosomes. A hematopathologist is a specialist who studies blood cell diseases by examining samples of blood and marrow cells and other tissues.
The hematopathologist looks for the following to identify JMML:
- A persistent high level of monocytes in the blood (greater than 1,000 microliters of blood)
- No indication of the Philadelphia (Ph) chromosome or Bcr-Abl gene associated with chronic myeloid leukemia
- Less that 20 percent of blast cells in the blood and marrow
Some patients may also have:
- Moderate to severe anemia (caused by low red cell levels)
- Moderate to severe thrombocytopenia (caused by low platelet levels)
- Increased white cell levels, but not more than 100,000 microliters
About half of all JMML patients have certain changes to their red cells, including:
- Higher levels than normal (for the patient's age) of hemoglobin F
- Low levels of carbonic anhydrase, a protein found in the blood
- The appearance of the i antigen on the red cells' surface
About 85 percent of JMML patients have chromosomes that are abnormal in structure or number (cytogenetic abnormalities). Common cytogenetic abnormalities that affect JMML cells include:
- Monosomy 7 (chromosome 7 has one copy instead of the normal two) and other chromosome 7 abnormalities found in 25 percent to 30 percent of JMML patients.
- Damage to chromosomes 3 and 8, found in 5 percent to 10 percent of JMML patients.
- A mutation (change) within the gene family known as RAS, which affects about 25 percent of JMML patients.
- A mutation of the NF1 gene, which affects about 30 percent of JMML patients. The NF1 gene is normally associated with a rare genetic condition called neurofibromatosis 1. In neurofibromatosis 1, children may have coffee-colored spots and pea-sized tumors on their skin; freckling in skin areas not exposed to the sun; a tumor on the optic nerve that affects eyesight (optic glioma); and developmental problems in the nervous system, muscles and bones. Not all children who have the NF1 gene mutation develop neurofibromatosis 1, but children who have neurofibromatosis are about 500 times more likely to develop JMML or another myeloid disorder than children without the protein.
- A mutation of the PTPN11 gene, which affects about 35 percent of JMML patients. This mutation sometimes causes a condition called Noonan syndrome. Children with JMML who have the PTPN11 gene mutation may have features associated with Noonan syndrome such as heart malformation, short stature, learning disabilities, a chest indentation, impaired blood clotting and characteristic facial features.