Molecular biology techniques for assessing the loss of HLA heterozygosity after allogeneic hematopoietic stem cell transplantation in children with acute leukemia
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Published:2024-01-17
Issue:4
Volume:10
Page:25-33
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ISSN:2413-5496
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Container-title:Russian Journal of Pediatric Hematology and Oncology
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language:
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Short-container-title:Ross. ž. det. gematol. onkol.
Author:
Barkhatov I. M.1ORCID, Tsvetkova L. A.1ORCID, Evdokimov A. V.1ORCID, Ivanova N. E.1ORCID, Epifanovskaya O. S.1ORCID, Semenko Yu. G.1ORCID, Smirnov B. I.2, Kulagin A. D.1ORCID, Zubarovskaya L. S.1ORCID
Affiliation:
1. Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Ministry of Health of Russia 2. Saint Petersburg Electrotechnical University “LETI”, Ministry for Education and Science of the Russian Federation
Abstract
According to several observations, up to a third of post-transplant relapses in childhood acute leukemia are associated with the loss of heterozygosity of the major histocompatibility complex (HLA). Furthermore, the inefficacy of the graft-versus-leukemia reaction, as evidenced by the lack of therapeutic effect from the infusion of donor lymphocytes, indicates the need for timely detection of this marker to change the treatment strategy in the post-transplant period. To detect the loss of HLA heterozygosity, the method using the commercial KMR-HLA system and analysis using next-generation sequencing (NGS), as well as the method based on the analysis of highly polymorphic STR and VNTR markers located in the HLA loci region on the short arm of chromosome 6, are widely used. The primary objective of our study was to compare the informativeness of these approaches in diagnosing HLA heterozygosity loss in children during the post-transplant period. The obtained data on the frequency of detecting HLA heterozygosity loss were comparable to the literature data and constituted 23 % of cases of post-transplant relapse of B-cell acute lymphoblastic leukemia, 33 % of cases of T-cell acute lymphoblastic leukemia, and 23% of cases of acute myeloid leukemia. We also demonstrated that the method based on STR marker analysis has sensitivity comparable to allele-specific PCR and NGS sequencing methods. Meanwhile, preliminary sorting of the blast population increases the sensitivity of STR analysis and can be recommended in routine practice.
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