*Please note this programme is currently in the process of preparing for UKAS (ISO 17043) accreditation.
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. Two send-outs are issued per annum, with each send-out consisting of 2 samples. This is expected to increase to 3 send-outs per annum for the year 2021/22 onwards (subject to accreditation).
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.
To register for this programme, please click here.
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 reflect the preferred use of the term ‘variant’, please note a planned change of programme name. Upon successful ISO 17043 accreditation the official programme name will be ‘BCR-ABL1 Kinase Domain Variant Status’. However, some issued documentation during the pilot phase of this scheme will feature the historic programme name ‘BCR-ABL1 Kinase Domain Mutation Status’.