Sign in →

Test Code MISC BCR/ABL1, Tyrosine Kinase Inhibitor Resistance, Kinase Domain Mutation Screen, Sanger Sequencing

Important Note

Mayo test code BAKDM

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.

 

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

Performing Laboratory

Mayo Medical Laboratories in Rochester

Specimen Type

Varies


Advisory Information


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



Shipping Instructions


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


Note: 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.

 

Submit only 1 of the following specimens:

 

Preferred:

Specimen Type: Whole blood

Container/Tube: EDTA (lavender top)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

3. Label specimen as blood.

 

Acceptable:

Specimen Type: Bone marrow

Container/Tube: EDTA (lavender top)

Specimen Volume: 2 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

1 mL

Specimen Stability Information

Specimen Type Temperature Time
Varies Refrigerated (preferred) 5 days
  Ambient  72 hours

Reference Values

An interpretive report will be provided.

Day(s) and Time(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 U.S. 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 In Process

 

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).

Analytic Time

5 days

NY State Approved

Yes

Method Name

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

Forms

1. Hematopathology Patient Information (T676) in Special Instructions

2. If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request Form (T726) with the specimen (http://www.mayomedicallaboratories.com/it-mmfiles/hematopathology-request-form.pdf)