Timo I. Olieslagers, Mathijs Groeneweg, Gwendolyn N. Y. van Gorkom, Erik A. M. Beckers, Lotte Wieten, Christina E. M. Voorter
Tumour cells, which are often found in the peripheral blood of patients with acute leukaemia, may harbour multiple somatic alterations throughout the genome, including changes in the HLA region and short tandem repeat (STR) regions. We investigated whether such somatic alterations interfere with HLA and chimerism diagnostics conducted in preparation for an allogeneic haematopoietic stem cell transplantation (allo-HSCT). This study describes 10 patient-based cases for which laboratory diagnostics were performed prior to a possible stem cell transplant in the Maastricht University Medical Center. In three acute leukaemia patients, somatic alterations were detected within the HLA region in peripheral blood samples: one case showed a complete loss of an HLA haplotype, while two cases exhibited somatic mutations affecting a single HLA class I gene. Additionally, seven patients with haematological malignancies revealed somatic variations within the STR regions, indicated by the presence of a third allele or the partial or complete loss of an allele in pre-transplant peripheral blood samples. In all patients, these somatic variations were confirmed by repeating the tests using buccal swab samples from patients or samples from family members. Furthermore, our study demonstrated that somatic alterations within STR regions used for chimerism testing occurred in 6% of the 176 patients who received an allo-HSCT between 2017 and 2022. This study underscores the clinical relevance of detecting somatic alterations prior to allo-HSCT, as they may interfere with HLA and STR analysis, potentially leading to HLA mistyping or incorrect chimerism detection. Additionally, it highlights the frequency with which genetic changes in tumour cells can affect chimerism diagnostics. The findings emphasise the vital importance of selecting the appropriate sample source for typing purposes and considering the patient's karyotype when choosing STRs, especially when tumour cells are present in the peripheral blood of patients with haematological malignancies.
{"title":"Somatic Genomic Alterations in Haematological Tumours Can Interfere With Accurate HLA and Chimerism Diagnostics","authors":"Timo I. Olieslagers, Mathijs Groeneweg, Gwendolyn N. Y. van Gorkom, Erik A. M. Beckers, Lotte Wieten, Christina E. M. Voorter","doi":"10.1111/tan.70093","DOIUrl":"https://doi.org/10.1111/tan.70093","url":null,"abstract":"<p>Tumour cells, which are often found in the peripheral blood of patients with acute leukaemia, may harbour multiple somatic alterations throughout the genome, including changes in the HLA region and short tandem repeat (STR) regions. We investigated whether such somatic alterations interfere with HLA and chimerism diagnostics conducted in preparation for an allogeneic haematopoietic stem cell transplantation (allo-HSCT). This study describes 10 patient-based cases for which laboratory diagnostics were performed prior to a possible stem cell transplant in the Maastricht University Medical Center. In three acute leukaemia patients, somatic alterations were detected within the HLA region in peripheral blood samples: one case showed a complete loss of an HLA haplotype, while two cases exhibited somatic mutations affecting a single HLA class I gene. Additionally, seven patients with haematological malignancies revealed somatic variations within the STR regions, indicated by the presence of a third allele or the partial or complete loss of an allele in pre-transplant peripheral blood samples. In all patients, these somatic variations were confirmed by repeating the tests using buccal swab samples from patients or samples from family members. Furthermore, our study demonstrated that somatic alterations within STR regions used for chimerism testing occurred in 6% of the 176 patients who received an allo-HSCT between 2017 and 2022. This study underscores the clinical relevance of detecting somatic alterations prior to allo-HSCT, as they may interfere with HLA and STR analysis, potentially leading to HLA mistyping or incorrect chimerism detection. Additionally, it highlights the frequency with which genetic changes in tumour cells can affect chimerism diagnostics. The findings emphasise the vital importance of selecting the appropriate sample source for typing purposes and considering the patient's karyotype when choosing STRs, especially when tumour cells are present in the peripheral blood of patients with haematological malignancies.</p>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"105 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/tan.70093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HLA-B*27:284 differs from HLA-B*27:07:01 by one nucleotide substitution in exon 4, at gDNA position 1614 (G>A).
{"title":"Discovery of the Novel HLA-B*27:284 Allele Identified by Next Generation Sequencing","authors":"Justine Schmitt, André Gothot","doi":"10.1111/tan.70130","DOIUrl":"https://doi.org/10.1111/tan.70130","url":null,"abstract":"<div>\u0000 \u0000 <p>HLA-B*27:284 differs from HLA-B*27:07:01 by one nucleotide substitution in exon 4, at gDNA position 1614 (G>A).</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"105 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The novel HLA-DQB1*05:03:38 allele was first described in a Chinese individual.
{"title":"Characterisation of the Novel HLA-DQB1*05:03:38 Allele Using Next-Generation Sequencing","authors":"Zhan-Rou Quan, Si-Qi Cai","doi":"10.1111/tan.70118","DOIUrl":"https://doi.org/10.1111/tan.70118","url":null,"abstract":"<div>\u0000 \u0000 <p>The novel <i>HLA-DQB1*05:03:38</i> allele was first described in a Chinese individual.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"105 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mirzokhid Rakhmanov, Martin Bernheiden, Murielle Verboom, Michael Hallensleben, Florian Emmerich
HLA-B*51:01:01:125 differs from HLA-B*51:01:01:61 by a single substitution at the genomic nucleotide position 199 in intron 1.
{"title":"Characterisation of a Novel HLA-B*51:01:01:125 Allele by Next-Generation Sequencing","authors":"Mirzokhid Rakhmanov, Martin Bernheiden, Murielle Verboom, Michael Hallensleben, Florian Emmerich","doi":"10.1111/tan.70131","DOIUrl":"https://doi.org/10.1111/tan.70131","url":null,"abstract":"<div>\u0000 \u0000 <p>HLA-B*51:01:01:125 differs from HLA-B*51:01:01:61 by a single substitution at the genomic nucleotide position 199 in intron 1.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"105 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jianing Yuan, Bin Xi, Xin Li, Zechang Shi, Mingrui Huo
The HLA-A*02:1178 allele differs from HLA-A*02:07:01:01 by one nucleotide substitution in codon 326 in exon 7.
{"title":"Characterisation of the Novel HLA-A*02:1178 Allele Using Next-Generation Sequencing Methods","authors":"Jianing Yuan, Bin Xi, Xin Li, Zechang Shi, Mingrui Huo","doi":"10.1111/tan.70132","DOIUrl":"https://doi.org/10.1111/tan.70132","url":null,"abstract":"<div>\u0000 \u0000 <p>The HLA-A*02:1178 allele differs from HLA-A*02:07:01:01 by one nucleotide substitution in codon 326 in exon 7.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"105 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adèle Dhuyser, Michaël Pérès, Thomas Morel, Sandra Clément, Alice Aarnink
The novel allele HLA-DQA1*05:89 differs from HLA-DQA1*05:05:01:01 by one non-synonymous nucleotide substitution in exon 2.
{"title":"The Novel HLA-DQA1*05:89 Allele Characterised by Two Different Sequencing-Based Typing Techniques","authors":"Adèle Dhuyser, Michaël Pérès, Thomas Morel, Sandra Clément, Alice Aarnink","doi":"10.1111/tan.70099","DOIUrl":"https://doi.org/10.1111/tan.70099","url":null,"abstract":"<div>\u0000 \u0000 <p>The novel allele <i>HLA-DQA1*05:89</i> differs from <i>HLA-DQA1*05:05:01:01</i> by one non-synonymous nucleotide substitution in exon 2.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"105 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mirzokhid Rakhmanov, Martin Bernheiden, Murielle Verboom, Michael Hallensleben, Florian Emmerich
HLA-C*15:02:01:69Q differs from HLA-C*15:02:01:01 by a single substitution at the genomic nucleotide position 2727 in intron 7.
{"title":"HLA-C*15:02:01:69Q, A New Allele With A Different Splice Site","authors":"Mirzokhid Rakhmanov, Martin Bernheiden, Murielle Verboom, Michael Hallensleben, Florian Emmerich","doi":"10.1111/tan.70126","DOIUrl":"https://doi.org/10.1111/tan.70126","url":null,"abstract":"<div>\u0000 \u0000 <p>HLA-C*15:02:01:69Q differs from HLA-C*15:02:01:01 by a single substitution at the genomic nucleotide position 2727 in intron 7.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"105 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuan Yuan Jing, Dong Mei Li, Na Liu, Yan Jun Jia, Tie Cheng Sun
The HLA-A*02:07:01:07 allele differs from HLA-A*02:07:01:01 by a single nucleotide change in intron 3.
{"title":"Recognition of the Novel HLA-A*02:07:01:07 Allele Through Third-Generation HLA-Targeted Sequencing Technology","authors":"Yuan Yuan Jing, Dong Mei Li, Na Liu, Yan Jun Jia, Tie Cheng Sun","doi":"10.1111/tan.70120","DOIUrl":"https://doi.org/10.1111/tan.70120","url":null,"abstract":"<div>\u0000 \u0000 <p>The HLA-A*02:07:01:07 allele differs from HLA-A*02:07:01:01 by a single nucleotide change in intron 3.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"105 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The full genomic sequence shows HLA-A*02:07:08 differs from HLA-A*02:07:01:01 only at position 131 in exon 3.
{"title":"The Full-Length Genomic Sequence of the HLA-A*02:07:08 Allele","authors":"Wei Tian, LiXin Li","doi":"10.1111/tan.70117","DOIUrl":"https://doi.org/10.1111/tan.70117","url":null,"abstract":"<div>\u0000 \u0000 <p>The full genomic sequence shows HLA-A*02:07:08 differs from HLA-A*02:07:01:01 only at position 131 in exon 3.</p>\u0000 </div>","PeriodicalId":13172,"journal":{"name":"HLA","volume":"105 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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