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Test ID: BAKDM BCR/ABL1, Tyrosine Kinase Inhibitor Resistance, Kinase Domain Mutation Screen, Sanger Sequencing, Varies

Reporting Name

BCR/ABL1 Mutation, Sequencing

Useful For

Evaluating patients with chronic myelogenous leukemia and Philadelphia chromosome positive B-cell acute lymphoblastic leukemia receiving tyrosine kinase inhibitor (TKI) therapy, who are apparently failing treatment


Preferred initial test to identify the presence of acquired BCR-ABL1 mutations associated with TKI-resistance

Testing Algorithm

If BCR/ABL1 fusion type (p210, p190, p205 or p230) is not provided, BADX / BCR/ABL1, Qualitative, Diagnostic Assay will be performed at an additional charge.


In the event that no fusion form (p190, p205, p210, p230) is identified by BADX testing, BAKDM testing will be cancelled.


This is the preferred initial test to identify the presence of acquired BCR/ABL1 mutations associated with TKI-resistance.


See BCR/ABL1 Ordering Guide for Blood and Bone Marrow in Special Instructions.

Specimen Type


Ordering Guidance

This is the preferred initial test to identify the presence of acquired BCR/ABL1 mutations associated with tyrosine kinase inhibitor (TKI)-resistance.

Shipping Instructions

1. Refrigerated specimens must arrive within 5 days (120 hours) of collection, and ambient specimens must arrive within 3 days (72 hours) of collection.

2. Draw and package specimen as close to shipping time as possible.

Necessary Information

The following information is required:

1. Patient's fusion type (p210, p190, p205 or p230)

2. Pertinent clinical history

3. Clinical or morphologic suspicion

4. Date of collection

5. Specimen source (blood or bone marrow)

Specimen Required

Submit only 1 of the following specimens:



Specimen Type: Whole blood

Container/Tube: EDTA (lavender top)

Specimen Volume: 10 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

3. Label specimen as blood.



Specimen Type: Bone marrow

Container/Tube: EDTA (lavender top)

Specimen Volume: 4 mL

Collection Instructions:

1. Invert several times to mix bone marrow.

2. Send specimen in original tube.

3. Label specimen as bone marrow.

Specimen Minimum Volume

Blood: 4 mL
Bone Marrow: 2 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Refrigerated (preferred) 5 days PURPLE OR PINK TOP/EDTA
  Ambient  72 hours PURPLE OR PINK TOP/EDTA

Reference Values

An interpretive report will be provided.

Day(s) Performed

Monday through Friday

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

81170-ABL1 (ABL proto-ongogene 1, non-receptor tyrosine kinase)(eg, acquired imatinib tyrosine kinase inhibitor resistance), gene analysis, variants in the kinase domain

LOINC Code Information

Test ID Test Order Name Order LOINC Value
BAKDM BCR/ABL1 Mutation, Sequencing 55135-8


Result ID Test Result Name Result LOINC Value
MP004 Specimen Type 31208-2
MOFF BCRABL Fusion (210, 190, 205, 230) 55135-8
19824 Final Diagnosis: 34574-4

Clinical Information

Chronic myelogenous leukemia (CML) is characterized by the presence of the t(9:22) BCR/ABL1 abnormality, resulting in formation of a fusion BCR/ABL1 mRNA and protein. The ABL1 component of this oncoprotein contains tyrosine kinase activity and is thought to play a central role in the proliferative phenotype of this leukemia.


Recent advances have resulted in a number of therapeutic drugs that inhibit the ABL1 tyrosine kinase, as well as other protein tyrosine kinases. Imatinib mesylate (Gleevec, Novartis) is the prototype of these tyrosine kinase inhibitors (TKIs), which are capable of inducing durable hematologic and (in most patients) cytogenetic remissions. Unfortunately, a significant subset of patients can develop functional resistance to TKIs, due in a large number of cases (approximately 50%) to the acquisition of point mutations in the kinase domain (KD) of the chimeric ABL1 gene. To date, over 50 distinct mutations have been described, although a smaller subset of these (<20) account for the majority of patients with clinical resistance to TKIs, or have well documented in vitro data in the published literature.


Recognition of TKI resistance is important in CML, as the effect of some mutations can be overcome by increasing imatinib dosage, whereas others require switching to either a different (second-generation) TKI, or alternative therapy. The common T315I KD mutation is particularly important, given that this alteration confers pan-resistance to all currently employed TKIs except ponatinib. Typically, TKI resistance is suspected in a CML patient who shows loss of initial therapeutic response (eg, cytogenetic relapse), or a significant and sustained increase in molecular BCR/ABL1 quantitative levels. Similar considerations are also present in patients with Philadelphia chromosome positive B-cell acute lymphoblastic leukemia, who can also be treated using TKI therapy.


Point mutations in the oncogenic BCR/ABL1 are typically detected by direct sequencing of PCR products, following RT-PCR amplification of the BCR/ABL mRNA transcript from a peripheral blood specimen. This approach ensures comprehensive screening of the clinically relevant KD region. Because this technique requires inclusion of a longer region of ABL1 in the BCR/ABL1 RT-PCR product, low levels of the BCR/ABL1 mRNA transcript (below 0.01% normalized BCR/ABL1 on the International Scale: IS) may not be efficiently amplified (in contrast to similar amplicons generated by quantitative RT-PCR for diagnosis or monitoring).


The presence of one or more point mutations in the translocated portion of the ABL1 region of the BCR/ABL1 fusion mRNA is considered a positive result, indicating tyrosine kinase inhibitor (TKI) resistance. The specific type of mutation may influence the sensitivity to a specific TKI, and could be useful in guiding therapeutic options for an individual patient.

Clinical Reference

1. Hughes T, Deininger M, Hochhaus A, et al: Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 2006;108:28-37

2. Press RD, Kamel-Reid S, Ang D: BCR-ABL1 RT-qPCR for Monitoring the Molecular Response to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia. J Mol Diagn 2013;15:565-576

3. Baccarani M, Deininger MW, Rosti G, et al: European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 2013;122:872-884

4. Jones D, Kamel-Reid S, Bahler D, et al: Laboratory practice guidelines for detecting and reporting BCR-ABL drug resistance mutations in chronic myelogenous leukemia and acute lymphoblastic leukemia A Report of the Association for Molecular Pathology. J Mol Diagn 2009;11:4-11

Report Available

5 days

Method Name

Reverse Transcription-Polymerase Chain Reaction (RT-PCR) with Analysis of PCR Products by Sanger Sequencing


1. Hematopathology Patient Information (T676) in Special Instructions

2. If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
BADX BCR/ABL1, RNA-Qual, Diagnostic Yes No
Mayo Clinic Laboratories | Hematology Catalog Additional Information: