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Introduction: Role of Genetic Testing in CML

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Chronic myeloid leukemia (CML) was the first disease to be associated with a clear genetic abnormality, the Philadelphia (Ph) chromosome, which is the hallmark of this disease. The presence of the Ph chromosome’s fusion gene, BCR-ABL, guides treatment decision making. In addition, mutations can occur in the BCR-ABL kinase domain, which can later serve as a model for adjusting therapy and, hopefully in the future, developing more precise medicine. It’s important for clinicians to understand how and when to conduct mutational analysis testing.

Stuart Goldberg, MD, explains the importance of confirming CML by testing for the Ph chromosome with a bone marrow cytogenetic analysis. He also recommends baseline polymerase chain reaction (PCR) from the peripheral blood for the BCR-ABL fusion protein, explaining that some patients may be Ph chromosome-positive by genetics, but do not have the marker in their blood. This baseline data can also be used during treatment to gauge response and the need for therapeutic adjustments.

Neil P. Shah, MD, adds that approximately 1% to 2% of patients will have an atypical BCR-ABL transcript, simply because of where the chromosome breakpoint occurs. This is an important fact to know, especially if no baseline test is completed. Oncologists may be falsely lulled into thinking that undetectable BCR-ABL at a patient’s first time check after starting treatment reflects a deep molecular response, when, in fact, there may be no molecular response whatsoever. He explains that it is not necessary to do mutation testing prior to therapy since there may be risk of picking up an artifact. However, testing is advised if a patient has progressed from chronic to accelerated or blast phase on tyrosine-kinase inhibitor (TKI) therapy.

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