BCR-ABL1 Kinase Domain Mutation Analysis

TEST: 480510
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CPT: 81170
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Synonyms

  • ABL1 Mutation Analysis for Resistance to Imatinib Mesylate
  • Gleevec Resistance Mutation Analysis
  • Imatinib Mesylate Resistance Analysis

Special Instructions

Please direct any questions regarding this test to oncology customer service at 800-345-4363.

Expected Turnaround Time

10 - 14 days

Turnaround time is defined as the usual number of days from the date of pickup of a specimen for testing to when the result is released to the ordering provider. In some cases, additional time should be allowed for additional confirmatory or additional reflex tests. Testing schedules may vary.

Related Information

Related Documents

Specimen Requirements

Specimen

Whole blood or bone marrow

Volume

3 to 5 mL whole blood or 1 to 2 mL bone marrow

Minimum Volume

3 mL whole blood or 1 mL bone marrow

Container

Lavender-top (EDTA) tube, green-top (sodium heparin) tube, yellow-top (ACD-A) tube, tan-top (K2-EDTA) tube or pink-top (K2-EDTA) tube

Collection

Submit at room temperature. Specimens should arrive in the laboratory within 48 hours of collection. Indicate date and time of collection on request form.

Storage Instructions

Ship at room temperature. If specimen must be stored prior to shipment, store at 2°C to 8°C.

Causes for Rejection

Specimen does not meet all of the above criteria for sample type, container, minimum volume, collection and storage; unsuitable specimens include but are not limited to: frozen whole blood or marrow; a leaking tube; clotted blood or marrow; a grossly hemolyzed specimen or otherwise visibly degraded; specimen suspected of being contaminated by another specimen; specimen contains specific foreign material

Test Details

Use

Point mutations within the ABL1 kinase domain of the BCR-ABL1 fusion gene frequently cause secondary resistance to tyrosine kinase inhibitor (TKI) therapy. Those patients with a longer duration of CML prior to initiation of imatinib therapy are reported to have a higher incidence of detectable mutations compared to patients with an earlier onset of imatinib therapy. In addition, failure to achieve a major cytogenetic response within the first six months of therapy often reflects the presence of a mutation or a high probability that a mutation will subsequently be detected. Biochemical and cellular assays have demonstrated that the different BCR-ABL1 kinase domain mutations result in varying levels of resistance. Presence of kinase domain mutations are associated with poor prognosis and higher risk of disease progression. The different mutations may require differing strategies to overcome resistance, such as dose escalation, combination therapy or transplantation. Candidates for the BCR-ABL1 kinase domain mutation analysis include:

• Response milestones not reached

· Any sign of loss of hematologic response

· Any sign of loss of Complete cytogenetic response (CCyR) or its molecular response correlate-defined as an increase in BCR::ABL1 transcript to >1% International scale [IS]

· 1-log increase in BCR::ABL1 transcript levels and loss of Major Molecular Response (MMR)

• Disease progression to Accelerated Phase (AP-CML) or Blast Phase (BP-CML)

This assay sequences the entire ABL1 kinase domain and will detect all mutations in ABL1 kinase recommended by guidelines including G250E, Y253H, E255K/V, V299L, T315I/A, F317L/V/I/C, A337T, F359V/I/C and P465S.

Limitations

In vitro studies indicate that this analysis has a mutation detection sensitivity of ∼20%. Mutations occurring outside of the analyzed region of the ABL kinase domain will also not be detected by this assay.

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

Methodology

Polymerase chain reaction (PCR); direct sequencing; capillary electrophoresis

References

Branford S, Rudzki Z, Parkinson I, et al. Real-time quantitative PCR analysis can be used as a primary screen to identify patients with CML treated with imatinib who have BCR-ABL kinase domain mutations. Blood. 2004 Nov 1; 104(9):2926-2932.15256429
Branford S, Rudzki Z, Walsh S, et al. Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-Loop) are associated with a poor prognosis. Blood. 2003 Jul 1; 102(1):276-283.12623848
Goldman J. Monitoring minimal residual disease in BCR-ABL-positive chronic myeloid leukemia in the imatinib era. Curr Opin Hematol. 2005 Jan; 12(1):33-39.15604889
National Comprehensive Cancer Network (NCCN). NCCN Guidelines: Chronic Myeloid Leukemia. Version 1.2024. NCCN website: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1427. Accessed November 2023.
Soverini S, Martinelli G, Rosti G, et al. ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: A study by the GIVEMA Working Party on Chronic Myeloid Leukemia. J Clin Oncol. 2005 Jun 20; 23(18):4100-4109.15867198

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
480510 BCR-ABL1 kinase domain 480511 Result: 55135-8
480510 BCR-ABL1 kinase domain 480512 Nucleotide Change: 48004-6
480510 BCR-ABL1 kinase domain 480513 Predicted Amino Acid Change: 48005-3
480510 BCR-ABL1 kinase domain 480843 Interpretation: 50398-7
480510 BCR-ABL1 kinase domain 480844 Methodology: 49549-9
480510 BCR-ABL1 kinase domain 481526 Disclaimer: N/A
480510 BCR-ABL1 kinase domain 480515 Director Review: 72486-4

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