Clinical Research Division, Department of Laboratory Medicine, University of Washington, Seattle, WA 98109, USA.
Hum Immunol. 2011 Jun;72(6):503-9. doi: 10.1016/j.humimm.2011.03.003. Epub 2011 Apr 2.
Clonal chromosomal abnormalities are often found in the tumor cells of patients with malignancies. These abnormalities can cause downregulation of human leukocyte antigen (HLA) and instability of short tandem repeat (STR) DNA sequences, confounding HLA typing and/or engraftment analysis in hematopoietic stem cell transplants (HSCT). We describe here the abnormalities observed during testing of 600 HSCT patients. HLA molecular typing was performed by reference strand conformational analyses and/or sequence-based typing. STR testing was performed with 10 to 16 STR primer sets, following 1 to 4 informative loci in each patient. Eight patients exhibited either loss of heterozygosity (4 STR, 3 HLA) or STR length mutation (n = 1), and 5 of the 8 exhibited correlative cytogenetic abnormalities. Diagnoses were acute myelogenous leukemia (AML; n = 7) or myelofibrosis (MFIB: n = 1), yielding an 11% incidence of these chromosomal abnormalities among the subset of 72 AML/MFIB HSCT patients. These results highlight some of the problems encountered and the possibility for interpretive errors that can arise when analyzing molecular typing and engraftment data, particularly among AML/MFIB patients.
克隆染色体异常在恶性肿瘤患者的肿瘤细胞中经常被发现。这些异常可导致人类白细胞抗原（HLA）的下调和短串联重复（STR）DNA 序列的不稳定性，从而干扰造血干细胞移植（HSCT）中的 HLA 分型和/或植入分析。我们在此描述了在对 600 名 HSCT 患者进行检测时观察到的异常情况。HLA 分子分型采用参考链构象分析和/或基于序列的分型进行。STR 测试采用 10 到 16 个 STR 引物组，每个患者检测 1 到 4 个信息性基因座。8 名患者表现出杂合性丢失（4 个 STR，3 个 HLA）或 STR 长度突变（n = 1），其中 5 名患者存在相关的细胞遗传学异常。诊断为急性髓系白血病（AML；n = 7）或骨髓纤维化（MFIB：n = 1），在 AML/MFIB HSCT 患者亚组的 72 名患者中，这些染色体异常的发生率为 11%。这些结果强调了在分析分子分型和植入数据时可能遇到的一些问题，以及可能出现的解释错误，尤其是在 AML/MFIB 患者中。
