دورية أكاديمية
Infant with diffuse large B-cell lymphoma identified postmortem with homozygous founder Slavic RAG1 variant: a case report and literature review.
| العنوان: | Infant with diffuse large B-cell lymphoma identified postmortem with homozygous founder Slavic RAG1 variant: a case report and literature review. |
|---|---|
| المؤلفون: | Volodashchik TP; Research Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus., Polyakova EA; Research Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus., Mikhaleuskaya TM; Research Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus., Sakovich IS; Research Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus., Kupchinskaya AN; Research Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus., Dubrouski AC; Pathological Unit, N.N. Alexandrov National Cancer Centre of Belarus, Lesnoy, Belarus., Belevtsev MV; Research Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus., Dasso JF; Division of Pediatric Allergy/Immunology, Johns Hopkins All Children's Hospital, Saint Petersburg, FL, United States.; Division of Pediatric Allergy/Immunology, University of South Florida, Tampa, FL, United States., Varabyou DS; Department of Geographical Ecology, Faculty of Geography and Geoinformatics, Belarusian State University, Minsk, Belarus., Notarangelo LD; Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIH), Bethesda, MD, United States., Walter JE; Division of Pediatric Allergy/Immunology, Johns Hopkins All Children's Hospital, Saint Petersburg, FL, United States.; Division of Pediatric Allergy/Immunology, University of South Florida, Tampa, FL, United States., Sharapova SO; Research Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus. |
| المصدر: | Frontiers in pediatrics [Front Pediatr] 2024 Jul 04; Vol. 12, pp. 1415020. Date of Electronic Publication: 2024 Jul 04 (Print Publication: 2024). |
| نوع المنشور: | Case Reports; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Media SA Country of Publication: Switzerland NLM ID: 101615492 Publication Model: eCollection Cited Medium: Print ISSN: 2296-2360 (Print) Linking ISSN: 22962360 NLM ISO Abbreviation: Front Pediatr Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Lausanne : Frontiers Media SA, [2013]- |
| مستخلص: | Background and Aims: There is an increased risk of lymphomas in inborn errors of immunity (IEI); however, germline genetic testing is rarely used in oncological patients, even in those with early onset of cancer. Our study focuses on a child with a recombination-activating gene 1 ( RAG1 ) deficiency who was identified through a screening program for Slavic founder genetic variants among patients who died with malignancy at an early age in Belarus. Results: We identified one homozygous founder RAG1 variant out of 24 available DNA samples from 71 patients who developed lymphoma aged <3 years from the Belarusian cancer registry between 1986 and 2023. Our patient had an episode of pneumonia at 3 months of age and was hospitalized for respiratory distress, candida-positive lung disease, and lymphadenopathy at 14 months of age. The diagnosis of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) was established. The patient had a normal lymphocyte count that decreased over time. One month after chemotherapy initiation, the patient died due to sepsis and multiple organ failure without a genetic diagnosis. In a retrospective analysis, T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) were undetectable in peripheral blood. Conclusions: A targeted screening program designed to detect a Slavic founder variant in the RAG1 gene among children revealed a 14-month-old Belarusian male infant with low TREC levels who died of EBV-driven DLBCL and complications of chemotherapy including infections. This case highlights how patients with IEI and recurrent infections may develop serious non-infectious complications, such as fatal malignancy. It also emphasizes the importance of early identification, such as newborn screening for severe combined immune deficiency. Earlier diagnosis of RAG deficiency could have prompted hematopoietic stem cell transplant well before the DLBCL occurrence. This likely would impact the onset and/or management strategies for the cancer. Competing Interests: LN is supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA (grant AI001222). JW is supported by National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA (grant # R01AI153830), Jeffrey Modell Foundation, and the Robert A. Good Endowment at the University of South Florida. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2024 Volodashchik, Polyakova, Mikhaleuskaya, Sakovich, Kupchinskaya, Dubrouski, Belevtsev, Dasso, Varabyou, Notarangelo, Walter and Sharapova.) |
| References: | Nat Rev Immunol. 2016 Apr;16(4):234-46. (PMID: 26996199) Front Immunol. 2022 Mar 24;13:863110. (PMID: 35401578) Pediatr Blood Cancer. 2018 Sep;65(9):e27258. (PMID: 29856523) Am J Hematol. 2011 Jan;86(1):48-55. (PMID: 21120868) Allergy Asthma Clin Immunol. 2022 Dec 12;18(1):106. (PMID: 36510326) N Engl J Med. 2008 May 8;358(19):2030-8. (PMID: 18463379) Cancer Res Commun. 2023 Nov 15;3(11):2312-2330. (PMID: 37910143) Cent Eur J Immunol. 2020;45(4):507-510. (PMID: 33658897) Viruses. 2014 Oct 23;6(10):4047-79. (PMID: 25341666) Cell Host Microbe. 2014 Mar 12;15(3):266-82. (PMID: 24629334) J Allergy Clin Immunol Pract. 2022 Jul;10(7):1725-1736.e2. (PMID: 35364342) Front Immunol. 2021 Jan 08;11:602482. (PMID: 33488600) J Pediatr. 1995 Jan;126(1):1-10. (PMID: 7815195) Acta Derm Venereol. 2018 Dec 27;99(1):105-106. (PMID: 30226529) Front Immunol. 2019 Apr 16;10:777. (PMID: 31057537) Blood. 2018 May 31;131(22):2454-2465. (PMID: 29650799) J Allergy Clin Immunol. 2018 Mar;141(3):1028-1035. (PMID: 28606585) J Allergy Clin Immunol. 2014 Apr;133(4):1099-108. (PMID: 24290284) Front Immunol. 2020 Nov 09;11:581119. (PMID: 33240268) Front Immunol. 2020 Jun 10;11:900. (PMID: 32655540) J Allergy Clin Immunol. 2018 Jan;141(1):59-68.e4. (PMID: 28669558) PLoS Genet. 2022 Oct 13;18(10):e1010421. (PMID: 36228010) Blood. 2018 May 31;131(22):2413-2425. (PMID: 29449275) J Pediatr Hematol Oncol. 2017 May;39(4):e203-e206. (PMID: 28267077) Immunogenetics. 2018 Sep;70(9):613-617. (PMID: 29492593) Curr Treat Options Oncol. 2016 Jul;17(7):33. (PMID: 27262707) Am J Dermatopathol. 2020 Jan;42(1):e11-e15. (PMID: 31313695) Curr Pediatr Rev. 2019;15(4):245-250. (PMID: 31530267) Front Oncol. 2022 Feb 14;12:790720. (PMID: 35237512) J Clin Invest. 2005 Nov;115(11):3140-8. (PMID: 16211094) |
| فهرسة مساهمة: | Keywords: RAG deficiency; case report; infant; lymphoma; malignancy in SCID |
| تواريخ الأحداث: | Date Created: 20240719 Latest Revision: 20240720 |
| رمز التحديث: | 20240720 |
| مُعرف محوري في PubMed: | PMC11254792 |
| DOI: | 10.3389/fped.2024.1415020 |
| PMID: | 39026935 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2296-2360 |
|---|---|
| DOI: | 10.3389/fped.2024.1415020 |