Relative quantitation of fusion transcripts resulting from t(9;22)(q34;q11.2) translocation with major (p210) BCR-ABL1 breakpoint Note: This test is not designed to detect fusion transcripts resulting from other BCR-ABL1 breakpoints such as the minor (p190) and the micro (p230) breakpoints (see Additional Information below).
Performing Laboratory / Facility
UCLA Medical Center Clinical Laboratory (CHS)
Performing Section
Molecular Pathology
Availability
Monday through Friday, 0700-1700
Turnaround Time
14 days from receipt of specimen in performing lab
Methodology
The QuantideX® qPCR BCR-ABL IS Kit is an in vitro nucleic acid amplification test for the relative quantitation of BCR-ABL1 and endogenous ABL1 transcripts in total RNA. It is a multiplex reverse transcription-quantitative RT-PCR hydrolysis probe technology performed on the Applied Biosystems 7500 Fast Dx Instrument.
Use
This test can be used to monitor response to therapy for disorders including chronic myeloid leukemia (CML) and B-lymphoblastic leukemia (B-ALL) in which a t(9 22)(q34 q11.2) reciprocal translocation with a major (p210) BCR-ABL1 breakpoint can be found.
The amount of RNA extracted may not be sufficient to perform the assay when the white blood count of the patient is very low. RNA is very labile significant degradation during collection or transport may result in assay failure. This test is only designed to detect e13a2 and e14a2 fusion transcripts resulting from a major (p210) BCR-ABL1 breakpoint. This test cannot distinguish between these two types of fusion transcripts. This test is not designed to detect fusion transcripts resulting from other BCR-ABL1 breakpoints such as the minor (p190) and the micro (p230) breakpoints.
Additional Information
The t(9 22)(q34 q11.2) reciprocal translocation, also known as the Philadelphia chromosome, fuses the 5' end of the BCR gene with the 3' end of the ABL1 gene leading to constitutive tyrosine kinase activity. This characteristic rearrangement is seen in approximately 90% to 95% of CML patients, 25% of adult B-ALL cases, and 2% to 4% of pediatric B-ALL cases1. Most patients in CML have a t(9 22) translocation with a major (p210) breakpoint involving intron 13 or intron 14 of the BCR gene and intron 1 of the ABL1 gene resulting in expression of the "e13a2" or "e14a2" fusion transcripts, respectively. Rarely, CML can show t(9 22) translocations with other breakpoints such as the minor (p190) breakpoint involving intron 1 of the BCR gene and intron 1 of ABL1 gene resulting in expression of the "e1a2" fusion transcript and the micro (p230) breakpoint resulting in expression of the "e19a2" fusion transcript. Due to alternative splicing, low levels of the e1a2 fusion transcript can be detected in some cases of CML with a major (p210) breakpoint 2,3. Unlike CML, the minor (p190) BCR-ABL fusion transcript is expressed by most pediatric cases of B-ALL. In contrast, approximately half of adult B-ALL cases produce the major (p210) BCR-ABL fusion transcript and the remainder the minor (p190) BCR-ABL fusion transcript1. Recommendations for BCR-ABL1 fusion transcript monitoring have been incorporated into recognized treatment guidelines4. Major molecular response (MMR), defined as 0.1%IS (MR3.0) on the International Scale, has been established as an important criterion in CML treatment4-7. [ref] 1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (eds). (2017). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Revised 4th Edition. Lyon, France: International Agency for Research on Cancer. [end ref][ref] 2. van Rhee F, Hochhaus A, Lin F, Melo JV, Goldman JM, Cross NC. p190 BCR-ABL mRNA is expressed at low levels in p210-positive chronic myeloid and acute lymphoblastic leukemias. Blood. 1996 Jun 15 87(12):5213-7. [end ref][ref] 3. Lichty BD, Keating A, Callum J, Yee K, Croxford R, Corpus G, Nwachukwu B, Kim P, Guo J, Kamel-Reid S. Expression of p210 and p190 BCR-ABL due to alternative splicing in chronic myelogenous leukaemia. Br J Haematol. 1998 Dec 103(3):711-5. [end ref][ref] 4. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Chronic Myelogenous Leukemia. v.1.2016. [end ref][ref] 5. Baccarani M, Druker BJ, Branford S et al. Long-term response to imatinib is not affected by the initial dose in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: final update from the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) study. Int J Hematol. 2014 99(5):616-624. [end ref][ref] 6. Hughes T, 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. [end ref][ref] 7. 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(5):565-576. [end ref]
Specimen Type
Whole Blood
Container
Lavender/EDTA
Volume
8mL
Minimum Volume
4 mL
Storage Temperature
Upon receipt at the Molecular Diagnostics Laboratories, store refrigerated at 2°C to 8°C for up to 96 hours from collection. Store extracted RNA at -80°C for 6 months.
Shipping and Handling Instructions
Transport specimen at room temperature or refrigerated at 2°C to 8°C.
No major (p210) BCR-ABL1 fusion transcript detected. If detected, a ratio of the major (p210) BCR-ABL1 fusion transcript level to the endogenous ABL1 transcript level is reported on an international scale (IS) along with a molecular reduction (MR) value.
Test Information
CPT Codes
81206
Synonyms
BCR-ABL
BCR/ABL
BCR-ABL1 Reciprocal Translocation
e13a2 and e14a2 Fusion Transcripts
Major (p210) Breakpoint
Philadelphia Chromosome
t(9
22)
Test Includes
Relative quantitation of fusion transcripts resulting from t(9;22)(q34;q11.2) translocation with major (p210) BCR-ABL1 breakpoint Note: This test is not designed to detect fusion transcripts resulting from other BCR-ABL1 breakpoints such as the minor (p190) and the micro (p230) breakpoints (see Additional Information below).
Performing Laboratory / Facility
UCLA Medical Center Clinical Laboratory (CHS)
Performing Section
Molecular Pathology
Availability
Monday through Friday, 0700-1700
Turnaround Time
14 days from receipt of specimen in performing lab
Methodology
The QuantideX® qPCR BCR-ABL IS Kit is an in vitro nucleic acid amplification test for the relative quantitation of BCR-ABL1 and endogenous ABL1 transcripts in total RNA. It is a multiplex reverse transcription-quantitative RT-PCR hydrolysis probe technology performed on the Applied Biosystems 7500 Fast Dx Instrument.
Use
This test can be used to monitor response to therapy for disorders including chronic myeloid leukemia (CML) and B-lymphoblastic leukemia (B-ALL) in which a t(9 22)(q34 q11.2) reciprocal translocation with a major (p210) BCR-ABL1 breakpoint can be found.
The amount of RNA extracted may not be sufficient to perform the assay when the white blood count of the patient is very low. RNA is very labile significant degradation during collection or transport may result in assay failure. This test is only designed to detect e13a2 and e14a2 fusion transcripts resulting from a major (p210) BCR-ABL1 breakpoint. This test cannot distinguish between these two types of fusion transcripts. This test is not designed to detect fusion transcripts resulting from other BCR-ABL1 breakpoints such as the minor (p190) and the micro (p230) breakpoints.
Additional Information
The t(9 22)(q34 q11.2) reciprocal translocation, also known as the Philadelphia chromosome, fuses the 5' end of the BCR gene with the 3' end of the ABL1 gene leading to constitutive tyrosine kinase activity. This characteristic rearrangement is seen in approximately 90% to 95% of CML patients, 25% of adult B-ALL cases, and 2% to 4% of pediatric B-ALL cases1. Most patients in CML have a t(9 22) translocation with a major (p210) breakpoint involving intron 13 or intron 14 of the BCR gene and intron 1 of the ABL1 gene resulting in expression of the "e13a2" or "e14a2" fusion transcripts, respectively. Rarely, CML can show t(9 22) translocations with other breakpoints such as the minor (p190) breakpoint involving intron 1 of the BCR gene and intron 1 of ABL1 gene resulting in expression of the "e1a2" fusion transcript and the micro (p230) breakpoint resulting in expression of the "e19a2" fusion transcript. Due to alternative splicing, low levels of the e1a2 fusion transcript can be detected in some cases of CML with a major (p210) breakpoint 2,3. Unlike CML, the minor (p190) BCR-ABL fusion transcript is expressed by most pediatric cases of B-ALL. In contrast, approximately half of adult B-ALL cases produce the major (p210) BCR-ABL fusion transcript and the remainder the minor (p190) BCR-ABL fusion transcript1. Recommendations for BCR-ABL1 fusion transcript monitoring have been incorporated into recognized treatment guidelines4. Major molecular response (MMR), defined as 0.1%IS (MR3.0) on the International Scale, has been established as an important criterion in CML treatment4-7. [ref] 1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (eds). (2017). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Revised 4th Edition. Lyon, France: International Agency for Research on Cancer. [end ref][ref] 2. van Rhee F, Hochhaus A, Lin F, Melo JV, Goldman JM, Cross NC. p190 BCR-ABL mRNA is expressed at low levels in p210-positive chronic myeloid and acute lymphoblastic leukemias. Blood. 1996 Jun 15 87(12):5213-7. [end ref][ref] 3. Lichty BD, Keating A, Callum J, Yee K, Croxford R, Corpus G, Nwachukwu B, Kim P, Guo J, Kamel-Reid S. Expression of p210 and p190 BCR-ABL due to alternative splicing in chronic myelogenous leukaemia. Br J Haematol. 1998 Dec 103(3):711-5. [end ref][ref] 4. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Chronic Myelogenous Leukemia. v.1.2016. [end ref][ref] 5. Baccarani M, Druker BJ, Branford S et al. Long-term response to imatinib is not affected by the initial dose in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: final update from the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) study. Int J Hematol. 2014 99(5):616-624. [end ref][ref] 6. Hughes T, 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. [end ref][ref] 7. 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(5):565-576. [end ref]
Specimen Collection and Handling
Specimen Type
Whole Blood
Container
Lavender/EDTA
Volume
8mL
Minimum Volume
4 mL
Storage Temperature
Upon receipt at the Molecular Diagnostics Laboratories, store refrigerated at 2°C to 8°C for up to 96 hours from collection. Store extracted RNA at -80°C for 6 months.
Shipping and Handling Instructions
Transport specimen at room temperature or refrigerated at 2°C to 8°C.
No major (p210) BCR-ABL1 fusion transcript detected. If detected, a ratio of the major (p210) BCR-ABL1 fusion transcript level to the endogenous ABL1 transcript level is reported on an international scale (IS) along with a molecular reduction (MR) value.
