Test Directory

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.

Specimen Type: Whole Blood

Alternate Specimen Type: Bone Marrow

Collection Container: Lavender Top (EDTA)

Alternate Collection Container: Green Top (Sodium or Lithium Heparin), Yellow Top (ACD), Tan Top (EDTA) or Pink Top (EDTA)

Desired Specimen Volume: 3 to 5 mL whole blood or 1 to 2 mL bone marrow

1. Collet a lavender top (EDTA) tube via venipuncture or follow bone marrow collection procedure.

1. Transport specimen in the original collection container.

Transport to the laboratory at room temperature. 

• Frozen whole blood or marrow
• Leaking tube
• Clotted blood or marrow
• Grossly hemolyzed specimen or otherwise visibly degraded
• Specimen suspected of being contaminated by another specimen
• Specimen contains specific foreign material

See patient report.

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.

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