TKI Resistance: ABL1 Gene Kinase Domain Mutation Analysis

Tyrosine kinase inhibitors (TKIs) are effective in treating t(9:22) positive CML and ALL. However, drug resistance may occur during the course of treatment due to the development of mutations in the kinase domain of ABL1 gene. Early detection of these mutations may prevent clinical relapse and allow the use of alternative tyrosine kinase inhibitors. NGS sequencing is used to detect mutations in the tyrosine kinase domain down to approximately 3% of the BCR::ABL1 fusion transcripts present in a patient sample. An mRNA transcript level of at least 1% IS (Major) or 1% NCN (minor) is required for sequencing to be successful.

Indications for Testing:

• Concern for possible primary failure to respond to TKIs after at least 3 months of treatment
• Significant increase in the Quantitative BCR::ABL transcripts while on treatment
• Disease progression to AP-CML or BP-CML

Sample Requirements:

2-3 mL whole blood or bone marrow in purple top EDTA tube

Sample Handling:

Sample should be kept cold, never frozen. This test is RNA based. RNA is very delicate and easily degraded. Do not delay in shipping as delay may affect results. For optimal results, fresh specimens should be shipped on the day of collection. Refrigerate specimens if held overnight.

Specimens being sent from outside facilities should be packaged according to standard medical safety practices. The specimen should be shipped by overnight priority [scheduled to arrive by Friday AM at the latest]. Use cold pack for overnight transport. Be sure cold pack is not in direct contact with specimen during transport.

Shipping Address:

Center for Human Genetics Laboratory
10524 Euclid Ave, 6th Floor
Cleveland, OH 44106
216-983-1134

For local samples, please call Client Service (216-844-5227) to arrange for sample pick-up.

Turn Around Time:

1 week

CPT codes

81170

Please submit a completed Hematology/Oncology Specimens requisition for each sample.