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 monocytes per microliter of blood [1,000/μl])
- No indication of the Philadelphia chromosome (Ph chromosome) or BCR-ABL gene rearrangement. The Ph chromosome is an abnormality of chromosome 22 found in the marrow and blood cells of patients with CML
- Less that 20 percent of blast cells in the blood and bone marrow
And at least 2 of the following criteria:
- Higher levels of hemoglobin F than is normal for the age of the patient
- Immature myeloid precursors in the blood
- Increased white blood cells (not more than 100,000 white blood cells per microliter of blood [100,000/μl]).
- Clonal cytogenetic abnormalities including monosomy 7
- Granulocyte-macrophage colony-stimulating factor (GM-CSF) hypersensitivity of myeloid progenitors.
About 85 percent of JMML patients have chromosomes that are abnormal in structure or number (cytogenetic abnormalities). Some of the cytogenetic abnormalities that have been noted in JMML patients include
- Monosomy 7 and other chromosome 7 abnormalities, which occur in approximately 25 to 30 percent of patients
- Abnormalities involving chromosomes 3 and 8, which occur in 5 to 10 percent of cases
- Mutations of the RAS family of genes, which occur in about 25 percent of patients
- A mutation of the NF1 gene. About 30 percent of JMML patients have the NF1 gene mutation and about 14 percent of JMML patients are also diagnosed with neurofibromatosis 1. Neurofibromatosis 1 is a rare genetic condition associated with coffee-colored spots and pea-sized tumors on the skin, freckling in skin areas not exposed to the sun, optic glioma (a tumor on the optic nerve that affects eyesight), and developmental abnormalities in the nervous system, muscles and bones. A child with neurofibromatosis 1 has about a 500-fold increased risk of developing JMML or another myeloid disorder.
- Mutation of the PTPN11 gene, which occurs in about 35 percent of patients. The genetic cause for Noonan syndrome is also a mutation of the PTPN11 gene. Children with JMML who have the PTPN11 gene mutation may have features associated with Noonan syndrome. These typically include heart malformation, short stature, learning disabilities, indentation of the chest, impaired blood clotting and facial changes.