Variant-specific BCR::ABL1 quantification discrepancy in chronic myeloid leukemia.
BCR‐ABL
CML
minimal residual disease
Journal
International journal of laboratory hematology
ISSN: 1751-553X
Titre abrégé: Int J Lab Hematol
Pays: England
ID NLM: 101300213
Informations de publication
Date de publication:
05 Jun 2024
05 Jun 2024
Historique:
received:
11
10
2023
accepted:
02
05
2024
medline:
6
6
2024
pubmed:
6
6
2024
entrez:
6
6
2024
Statut:
aheadofprint
Résumé
Accurate quantification of the BCR::ABL1 fusion gene in whole blood is pivotal for the clinical management of chronic myeloid leukemia (CML) patients. The fusion protein encoded by BCR::ABL1 can vary in size, depending on the BCR and/or ABL1 gene breakpoint. The vast majority of CML patients have a p210 BCR::ABL1 fusion gene (M-BCR), which can be attributed to the presence of either e14a2 (b3a2) or e13a2 (b2a2) mRNA transcript junctions. Twenty-five CML samples were analyzed in two different ISO15189-accredited centers that both use an Europe Against Cancer-based quantitative polymerase chain reaction (qPCR) protocol. Reanalysis of the sample set with transcript-specific standard curves and digital droplet PCR (ddPCR) were performed. qPCR quantification revealed a significant (up to 1 log) difference specifically for the e13a2 transcript variant in contrast to e14a2 transcripts (Hodges-Lehman 4.29; p < 0.001). Reanalysis of the sample set with transcript-specific standard curves abolishes the initial transcript-specific difference (Hodges-Lehman 0.003; p = 0.8192). Comparison of transcript-specific qPCR results of both centers with ddPCR, an absolute quantification method, showed a statically significant association, especially in the lower range, indicating the clinical utility of transcript-specific or absolute quantification methods. Our data show that differences between transcript-specific quantification might exist between centers, leading to potential clinical impact on the follow-up of CML patients. The use of transcript-specific standard curves for qPCR quantification, or absolute quantification, can significantly reduce these differences. Specific attention should be applied to the interpretation of quantification differences of CML patients that switch between diagnostic centers.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 John Wiley & Sons Ltd.
Références
Hochhaus A, Baccarani M, Silver RT, et al. European Leukemia Net 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34(34):966‐984.
Maes B, Bakkus M, Boeckx N, et al. A novel approach for BCR::ABL1 standardization to improve international scale estimation. Int J Lab Hematol. 2016;38:674‐684.
Soverini S, Bernardi S, Galimberti S. Molecular testing in CML between old and new methods: are we at a turning point? J Clin Med. 2020;9:3865.
Gabert J, Beillard E, van der Velden VHJ, et al. Standardization and quality control studies of ‘real‐time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia—a Europe Against Cancer program. Leukemia. 2003;7:2318‐2357.
Branford S, Fletcher L, Cross N, et al. Desirable performance characteristics for BCR::ABL measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trials. Blood. 2008;112:3330‐3338.
Cross N, White H, Ernst T, et al. Development and evaluation of a secondary reference panel for BCR::ABL1 quantification on the international scale. Leukemia. 2016;30:1844‐1852.
White H, Matejtschuk P, Rigsby P, et al. Establishment of the first World Health Organization International Genetic Reference Panel for quantitation of BCR‐ABL mRNA. Blood. 2010;116:111‐117.
Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2020 update on diagnosis. Therapy and monitoring. Am J Hematol. 2020;95:691‐709.
Hughes T, Kaeda J, Branford S, et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med. 2003;349:1423‐1432.
Cumbo C, Anelli L, Specchia G, Albano F. Monitoring of minimal residual disease (MRD) in chronic myeloid leukemia: recent advances. Cancer Manag Res. 2020;6:3175‐3189.
Kjaer L, Skov V, Morten T, et al. Variant‐specific discrepancy when quantitating BCR::ABL1 e13a2 and e14a2 transcripts using the Europe Against Cancer qPCR assay. Eur J Haematol. 2019;103:26‐34.
Pfirrmann M, Evtimova D, Saussele S, et al. No influence of BCR::ABL1 transcript types e13a2 and e14a2 on long‐term survival: results in 1494 patients with chronic myeloid leukemia treated with imatinib. J Cancer Res Clin Oncol. 2017;143:843‐850.
Jain P, Kantarjian H, Patel KP, et al. Impact of BCR::ABL transcript type on outcome in patients with chronic‐phase CML treated with tyrosine kinase inhibitors. Blood. 2016;127:1269‐1275.
Castagnetti F, Gugliotta G, Breccia M, et al. The BCR::ABL1 transcript type influences response and outcome in Philadelphia chromosome‐positive chronic myeloid leukemia patients treated frontline with imatinib. Am J Hematol. 2017;92:797‐805.
Bonifacio M, Scaffidi L, Binotto G, et al. Predictive factors of stable deep molecular response in chronic myeloid leukemia patients treated with imatinib standard dose: a study from the Gruppo Triveneto LMC. Blood. 2015;126:597.
Hanfstein B, Lauseker M, Hehlmann R, et al. Distinct characteristics of e13a2 versus e14a2 BCR‐ABL1 driven chronic myeloid leukemia under first‐line therapy with imatinib. Haematologica. 2014;99:1441‐1447.
Lucas CM, Harris RJ, Giannoudis A, et al. Chronic myeloid leukemia patients with the e13a2 BCR‐ABL fusion transcript have inferior responses to imatinib compared to patients with the e14a2 transcript. Haematologica. 2009;94:1362‐1367.
Bernardi S, Bonifacio M, Iurlo A, et al. Variant specific discrepancy when quantitating BCR::ABL1 e13a2 and e14a2 transcripts using the Europe Against Cancer qPCR assay. Is dPCR the key? Eur J Haematol. 2019;103:272‐273.
Dominy KM, Claudiani S, O'Hare M, et al. Assessment of quantitative polymerase chain reaction for BCR–ABL1 transcripts in chronic myeloid leukaemia: are improved outcomes in patients with e14a2 transcripts an artefact of technology? Br J Haematol. 2022;197:52‐62.
Huet S, Cony‐Makhoul P, Heiblig M, et al. Major molecular response achievement in CML patients can Be predicted by BCR::ABL1/ABL1 or BCR::ABL1/GUS ratio at an earlier time point of follow‐up than currently recommended. PLosOne. 2014;9(9):e106250.