BCR::ABL1 Kinase Domain Variant (Mutation) Status (Accredited)*

*Please note this programme has successfully achieved UKAS (ISO 17043) accreditation. Trial distribution KDV(M) 202101 (and onwards) will be formally scored and subject to performance monitoring as standard.

The introduction of tyrosine kinase inhibitors (TKIs), initially with imatinib and subsequently second and third generation TKIs, significantly changed the clinical management of patients with chronic myeloid leukaemia (CML) and to a degree those with Philadelphia positive (Ph+) acute lymphoblastic leukaemia (ALL).

Despite their clinical success, some patients experience progressive TKI resistance after an initial response. Over 100 different point mutations (variants) in the BCR::ABL1 kinase domain (KD) have been identified in CML and Ph+ ALL patients with TKI resistance. The detection of a subset of variants (mutations), with conclusive in vitro sensitivity and patient resistance profile evidence, plays an important role in therapeutic decision making; particularly when switching TKIs. Of note, the detection of the p.Thr315Ile (T315I) variant (mutation) is a poor prognosis marker conferring resistance to first and second generation TKIs.

For this programme participants are provided with lyophilised cell line based EQA material for BCR::ABL1 kinase domain variant (point mutation) status analysis using molecular methods. Laboratories are asked to submit (using Human Genome Variation Society (HGVS) recommended standardised sequence variant nomenclature) any clinically actionable BCR::ABL1 kinase domain variant(s) detected, along with details regarding their assay methodology. The programme is qualitative; however, optional quantitative information (‘mutation load’) may also be submitted for educational purposes.

Instructions for storage, reconstitution and use of the lyophilised samples are included with the distribution. Three send-outs are issued per annum, with each send-out consisting of 2 samples. An additional educational sample(s) featuring a ‘low level’ variant(s) (approximately 5-20% VAF), may be included in a given send-out; however, the result of this sample(s) will not be subject to performance monitoring at this time.

Fusion Gene Nomenclature - Latest Update 

Following the recent publication of the HUGO Gene Nomenclature committee (HGNC) consensus statement regarding fusion gene nomenclature (Bruford et al. 2021), UK NEQAS LI are working to implement use of the double colon (::) for the description of fusion genes (e.g. BCR::ABL1). Historical nomenclature (e.g. BCR-ABL1) may persist in some areas of our website and documentation for an interim period due to IT constraints.

Bruford EA, et al. HUGO Gene Nomenclature Committee (HGNC) recommendations for the designation of gene fusions. Leukemia. 2021 

Pre issue testing of samples for this programme is subcontracted, although the final decision about sample suitability lies with the EQA provider; no other activities in relation to this EQA programme are subcontracted.

We acknowledge Dr. Paul La Rosée (University of Jena), who kindly provided some of the initial cell line material for this programme.

Please note: The Human Genome Variation Society (HGVS) advocate no longer using the term ’mutation’ due to its variable definition in the fields of biology and medicine (https://varnomen.hgvs.org/bg-material/glossary/).

To register for this programme, please click here.