Olieslagers Timo I, Groeneweg Mathijs, van Gorkom Gwendolyn N Y, Beckers Erik A M, Wieten Lotte, Voorter Christina E M
Department of Transplantation Immunology, Maastricht University Medical Center, Maastricht, the Netherlands.
GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
HLA. 2025 Mar;105(3):e70093. doi: 10.1111/tan.70093.
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.
肿瘤细胞常见于急性白血病患者的外周血中，其整个基因组可能存在多种体细胞改变，包括HLA区域和短串联重复序列（STR）区域的变化。我们研究了这些体细胞改变是否会干扰为异基因造血干细胞移植（allo-HSCT）做准备时进行的HLA和嵌合状态诊断。本研究描述了10例基于患者的病例，这些病例在马斯特里赫特大学医学中心进行可能的干细胞移植前进行了实验室诊断。在3例急性白血病患者的外周血样本中检测到HLA区域内的体细胞改变：1例显示一个HLA单倍型完全缺失，2例表现出影响单个HLA I类基因的体细胞突变。此外，7例血液系统恶性肿瘤患者的STR区域存在体细胞变异，表现为移植前外周血样本中出现第三个等位基因或一个等位基因部分或完全缺失。在所有患者中，通过使用患者的口腔拭子样本或家庭成员的样本重复检测，证实了这些体细胞变异。此外，我们的研究表明，在2017年至2022年接受allo-HSCT的176例患者中，用于嵌合状态检测的STR区域内发生体细胞改变的比例为6%。本研究强调了在allo-HSCT前检测体细胞改变的临床相关性，因为它们可能干扰HLA和STR分析，可能导致HLA分型错误或嵌合状态检测错误。此外，它还突出了肿瘤细胞中的基因变化影响嵌合状态诊断的频率。这些发现强调了为分型目的选择合适样本来源以及在选择STR时考虑患者核型的至关重要性，尤其是当血液系统恶性肿瘤患者外周血中存在肿瘤细胞时。
