Diagnosing and Genomic Testing

An initial evaluation typically includes a symptom survey, physical exam, blood tests, a bone marrow biopsy, molecular and genetic testing, and imaging studies to evaluate the size of the liver and spleen.

Identifying any genetic mutations associated with myelofibrosis will be a part of the diagnostic process. Tests will examine a sample of tissue, blood or bone marrow to look for changes in chromosomes while molecular testing checks these samples for certain genes, proteins and other molecules that may have mutations (changes). More than one mutation, called a co-mutation, may be present.

Approximately half of patients with the disease have a mutation in the JAK2 gene, which is the most common mutation found in people with myelofibrosis. Most myelofibrosis mutations occur spontaneously and are not inherited from parents. If there are multiple people in the same family with myelofibrosis, you may be referred to a genetic counselor.

Other common mutations found in people with myelofibrosis include the calreticulin (CALR) gene and the myeloproliferative leukemia (MPL) gene. Other gene mutations that are associated with prognosis include ASXL1, EZH2, IDH1, IDH2, RAS, SF3B1, SRSF2, TET2 and U2AF1. The BCR-ABL1 gene is often tested to rule out chronic myeloid leukemia (CML).

Your doctor will assign a risk level to your myelofibrosis using a prognostic scoring system that is based on risk factors. High-risk myelofibrosis is more aggressive and may require more intense treatment.