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Licensed Unlicensed Requires Authentication Published by De Gruyter June 23, 2021

Development of an inverse-PCR approach for characterization of the major BCR-ABL1 breakpoint sequences on genomic DNA: proof of concept

  • Leandro G. Gutiérrez , Miguel M. Abelleyro , María Sol Ruiz , María Sol Anchordoqui , Josefina Freitas , Michele Bianchini , Carlos D. De Brasi and Irene B. Larripa EMAIL logo

Corresponding author: Dr. Irene B. Larripa, MSc, PhD, Instituto de Medicina Experimental (IMEX), CONICET-Academia Nacional de Medicina, Pacheco de Melo 3081 C1425AUM, Buenos Aires, Argentina, Phone: +5411 4809 1000, E-mail:
Leandro G. Gutiérrez and Miguel M. Abelleyro contributed equally to this work and should be considered first authors. Carlos D. De Brasi and Irene B. Larripa should be both considered senior authors.

Funding source: National Research Council (CONICET)

Funding source: National Agency for Scientific and Technological Promotion (ANPCyT)

Funding source: Foundation Alberto J. Roemmers

  1. Research funding: This study was supported by grants from the National Research Council (CONICET), National Agency for Scientific and Technological Promotion (ANPCyT) and Foundation Alberto J. Roemmers.

  2. Author contributions: All authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Peripheral blood samples from all CML patients were collected with written informed consent.

  5. Ethical approval: The research complied with all national regulations and institutional policies and was in accordance with the Helsinki Declaration. The research was approved by the Ethics Committee of the Institutes of the National Academy of Medicine of Buenos Aires, Argentina.

References

1. Fioretos, T, Bertil, F. Chapter 7: Chronic myeloid leukemia, In: Heim S, Mitelman F, editors. Cancer cytogenetics, 3rd ed. Hoboken, New Jersey: Wiley Blackwell, A John Wiley & Sons, Inc., Publication; 2009: 179–207 pp.10.1002/9781118010136.ch7Search in Google Scholar

2. Cross, NCP, White, HE, Colomer, D, Ehrencrona, H, Foroni, L, Gottardi, E, et al.. Laboratory recommendations for scoring deep molecular responses following treatment for chronic myeloid leukemia. Leukemia 2015;29:999–1003. https://doi.org/10.1038/leu.2015.29.Search in Google Scholar

3. Falchi, L, Kantarjian, H, Wang, X, Verma, D, Quintás-Cardama, A, O’Brien, S, et al.. Significance of deeper molecular responses in patients with chronic myeloid leukemia in early chronic phase treated with tyrosine kinase inhibitors. Am J Hematol 2013;88:1024–9. https://doi.org/10.1002/ajh.23560.Search in Google Scholar

4. Ross, DM, Branford, S, Seymour, JF, Schwarer, AP, Arthur, C, Bartley, PA, et al.. Patients with chronic myeloid leukemia who maintain a complete molecular response after stopping imatinib treatment have evidence of persistent leukemia by DNA PCR. Leukemia 2010;24:1719–24. https://doi.org/10.1038/leu.2010.185.Search in Google Scholar

5. Ross, DM, Hughes, TP. How I determine if and when to recommend stopping tyrosine kinase inhibitor treatment for chronic myeloid leukaemia. Br J Haematol 2014;166:3–11. https://doi.org/10.1111/bjh.12892.Search in Google Scholar

6. Pagani, IS, Dang, P, Kommers, IO, Goyne, JM, Nicola, M, Saunders, VA, et al.. BCR-ABL1 genomic DNA PCR response kinetics during first-line imatinib treatment of chronic myeloid leukemia. Haematologica 2018;103:2026–32. https://doi.org/10.3324/haematol.2018.189787.Search in Google Scholar

7. Score, J, Calasanz, MJ, Ottman, O. Analysis of genomic breakpoints in p190 and p210 BCR-ABL indicate distinct mechanisms of formation. Leukemia 2010;24:1742–50. https://doi.org/10.1038/leu.2010.174.Search in Google Scholar

8. Ross, DM, O’Hely, M, Bartley, PA, Dang, P, Score, J, Goyne, JM, et al.. Distribution of genomic breakpoints in chronic myeloid leukemia: analysis of 308 patients. Leukemia 2013;27:2105–7. https://doi.org/10.1038/leu.2013.116.Search in Google Scholar

9. Abelleyro, MM, Marchione, VD, Palmitelli, M, Radic, CP, Neme, D, Larripa, IB, et al.. Inverse PCR to perform long-distance haplotyping: main applications to improve preimplantation genetic diagnosis in hemophilia. Eur J Hum Genet 2019;27:603–11. https://doi.org/10.1038/s41431-018-0334-9.Search in Google Scholar

10. Mattarucchi, E, Guerini, V, Rambaldi, A, Campiotti, L, Venco, A, Pasquali, F, et al.. Microhomologies and interspersed repeat elements at genomic breakpoints in chronic myeloid leukemia. Genes Chromosomes Cancer 2008;47:625–32. https://doi.org/10.1002/gcc.20568.Search in Google Scholar

11. Alikian, M, Ellery, P, Forbes, M, Gerrard, G, Kasperaviciute, D, Sosinsky, A, et al.. Next-generation sequencing-assisted DNA-based digital PCR for a personalized approach to the detection and quantification of residual disease in chronic myeloid leukemia patients. J Mol Diagn 2016;18:176–89. https://doi.org/10.1016/j.jmoldx.2015.09.005.Search in Google Scholar

12. Polakova, KM, Zizkova, H, Zuna, J, Motlova, E, Hovorkova, L, Gottschalk, A, et al.. Analysis of chronic myeloid leukemia during deep molecular response by genomic PCR: a traffic light stratification model with impact on treatment-free remission. Leukemia 2020;34:2113–24. https://doi.org/10.1038/s41375-020-0882-1.Search in Google Scholar

13. Pagani, IP, Dang, P, Saunders, V, Grose, R, Shanmuganathan, N, Kok, C, et al.. Lineage of measurable residual disease in patients with chronic myeloid leukemia in treatment-free remission. Leukemia 2020;34:1052–61. https://doi.org/10.1038/s41375-019-0647-x.Search in Google Scholar

14. Sobrinho-Simoes, M, Wilczek, V, Score, J, Cross, NCP, Apperley, JF, Melo, JV. In search of the original leukemic clone in chronic myeloid leukemia patients in complete molecular remission after stem cell transplantation or imatinib. Blood 2010;116:1329–35. https://doi.org/10.1182/blood-2009-11-255109.Search in Google Scholar


Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2020-1482).


Received: 2020-10-06
Accepted: 2021-06-09
Published Online: 2021-06-23
Published in Print: 2021-11-25

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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