Diagnosing chronic myelomonocytic leukemia (CMML) usually involves a series of repeated tests, including blood and bone marrow tests. Your doctor usually can't confirm a diagnosis of CMML with one lab test result that shows abnormal blood counts. Instead, he or she will monitor you over a period of time with repeated lab tests that show abnormal blood counts. This is done to rule out other diagnoses.
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; and
- A bone marrow biopsy to remove a small amount of bone filled with marrow.
A hematopathologist examines the samples of your blood and marrow to confirm a diagnosis, identify the CMML subtype and look for damage to your chromosomes. A hematopathologist is a specialist who studies blood cell diseases by examining samples of blood cells, bone marrow cells and other tissues.
The hematopathologist looks for the following to identify CMML:
- Persistent high levels of monocytes in the blood (greater than 1,000 microliters of blood)
- No evidence of a Philadelphia chromosome (seen in a similar disease known as “chronic myeloid leukemia” (CML). This can be determined based on a blood test looking for a particular abnormality known as a BCR/ABL fusion gene.
- Less that 20 percent of blast cells in the blood and bone marrow
- Abnormal changes in any of the cells that develop into red blood cells, certain white blood cells or platelets (precursor cells)
Other Diagnostic Tests
Your doctor may order one or more tests such as those below to diagnose CMML:
- X-rays or computed tomography (CT) scans detect an enlarged spleen or liver.
- Blood and urine tests detect high levels of lysozyme, an enzyme found in saliva, tears and some immune cells like monocytes.
- Additional blood work looks for high levels of proteins called lactate dehydrogenase (LDH) and beta 2-microglobulin, which can indicate tissue damage and increased white-cell production or destruction caused by inflammation or certain types of cancer.
Twenty to forty percent of people with CMML have chromosomes that are abnormal in structure or number (called cytogenetic abnormalities). The hematopathologist examines blood for any chromosomal damage or rearrangements. Your doctor can use this information when designing your treatment plan.
Common cytogenetic abnormalities that affect CMML cells include:
- Abnormalities in Chromosome 7 and Chromosome 8. The most common chromosomal abnormalities in CMML patients involve chromosome 7 and chromosome 8. Most humans have 23 pairs of chromosomes, for a total of 46 chromosomes. In some cases of CMML, a copy of chromosome 7 is missing. In other cases, the patient has an extra copy of chromosome 8.
- A mutation (change) of a specific gene within the gene family known as RAS, such as K-RAS or N-RAS. RAS genes and the proteins they encode regulate cell growth. When a mutation (change) of a RAS gene occurs, cells multiply uncontrollably. This type of mutation occurs in approximately 35 percent of CMML patients.
A chromosome translocation involving the PDGFR-β and TEL genes. About 1 to 4 percent of CMML patients have an abnormality called a “translocation” (a piece of one chromosome breaks off and attaches to another chromosome, which can lead to the development of an “oncogene” (cancer-causing gene). In CMML sometimes the translocation involves the PDGFR-β and TEL genes. Patients who have the PDGFR-β and TEL gene mutations may respond favorably to treatment with the drug imatinib mesylate (Gleevec®).