BCR/ABL1, Tyrosine Kinase Inhibitor Resistance, Kinase Domain Mutation Screen, Sanger Sequencing, Varies

Casandra

Casandra Test Code MC55222Version 1 (DRAFT)

Performing Lab

Lab Mayo Clinic LabLab Test ID BAKDMCPT Code 81170

BCR/ABL1, Tyrosine Kinase Inhibitor Resistance, Kinase Domain Mutation Screen, Sanger Sequencing, Varies

Clinical Use

Use

This test is useful for evaluating patients with chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (ALL) who are receiving tyrosine kinase inhibitor (TKI) therapy and are apparently failing treatment. It is the preferred initial test to identify the presence of acquired BCR::ABL1 mutations associated with TKI-resistance, providing comprehensive screening of the clinically relevant kinase domain (KD) region.

Special Instructions

Refrigerated specimens must arrive within 5 days of collection, and ambient specimens must arrive within 3 days of collection. EDTA blood specimens are preferred for testing. Bone marrow specimens are acceptable, although there can be specimen failures due to bone marrow RNA. Heparin anticoagulant cannot be used due to PCR inhibition. Necessary information includes pertinent clinical history, including if the patient has a diagnosis of chronic myelogenous leukemia or other BCR::ABL1-positive neoplasm. Ambient specimens over 3 days old and refrigerated specimens over 5 days old at the time of receipt are unacceptable.

Limitations

This assay is comprehensive for detecting BCR::ABL1 kinase domain mutations but does not detect all possible mutations in ABL1. A negative result does not exclude the presence of a rare, less-well characterized, or unknown mutation that could be associated with TKI resistance. Subclonal mutations may be difficult to identify by Sanger sequencing due to its inherent sensitivity level limitation, which is typically around 15% to 20% mutant allele in a wild-type background. The BCR::ABL1 quantitative level should be above 0.1% for successful mutation detection.

Test Details

New York Approved