Overview
CML is a blood-based malignant disease defined by the presence of the Philadelphia (Ph) Chromosome in the leukemic cells as a result of a translocation between chromosomes 9 and 22 t(9;22). The Ph+ cells harbor a fusion oncogene know as BCR-ABL.1 The gene encodes the fusion protein known as p210BCR-ABL which leads to deregulated tyrosine kinase activity and cellular proliferation.
About 5,000 people are diagnosed with CML each year and about 25,000 people are currently living with the disease.
Current Treatment Options
The advent of BCR-ABL tyrosine kinase inhibitors earlier in this decade has completely changed the treatment and prognosis of CML patients. The current first line treatment known as imatinib (Gleevec®, Novartis) has demonstrated extremely high and robust response rates with 87% of patients reaching complete cytogentic response. 98% of those patients who reach Major Molecular Response (MMR) within 12 months remain in remission after 5 years.2
Benefits of Molecular Testing
Unfortunately, CML is not completely eradicated with BCR-ABL inhibitors and thus a risk of relapse remains for all patients. One of the major causes for relapse is imatinib resistance due to point mutation in the ABL domain. These mutations translate to lower binding affinities of the drug to the active site.
Therefore, patients must be monitored regularly for changes in BCR-ABLmRNA transcript levels and if transcripts levels rise, patients are often tested for the presence of ABL domain mutations to help direct the best course of therapy either with second line tyrosine kinase inhibitors (dasatinib, nilotinib) or bone marrow transplant.
MolecularMD is a world leader in molecular testing related to CML and tyrosine kinase inhibitor therapy. Click here for related tests.
1Shtivelman E, et al. Nature. 1985;315:550-4.
2Hughes T, et al. N Engl J Med. 2003;349:1423-1432.