Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway;
Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Cancer Genomics Proteomics. 2023 Jul-Aug;20(4):354-362. doi: 10.21873/cgp.20387.
BACKGROUND/AIM: Acute undifferentiated leukemia (AUL) is leukemia which does not express lineage-specific antigens. Such cases are rare, accounting for 2.7% of all acute leukemia. The reported genetic information of AULs is limited to less than 100 cases with abnormal karyotypes and a few cases carrying chimeric genes or point mutation of a gene. We herein present the genetic findings and clinical features of a case of AUL.
Bone marrow cells obtained at diagnosis from a 31-year-old patient with AUL were genetically investigated. G-Banding karyotyping revealed an abnormal karyotype: 45,X,-Y,t(5;10)(q35;p12),del(12)(p13)[12]/46,XY[5]. Array comparative genomic hybridization examination confirmed the del(12)(p13) seen by G-banding but also detected additional losses from 1q, 17q, Xp, and Xq corresponding to the deletion of approximately 150 genes from these five chromosome arms. RNA sequencing detected six HNRNPH1::MLLT10 and four MLLT10::HNRNPH1 chimeric transcripts, later confirmed by reverse-transcription polymerase chain reaction together with Sanger sequencing. Fluorescence in situ hybridization analysis showed the presence of HNRNPH1::MLLT10 and MLLT10::HNRNPH1 chimeric genes.
To the best of our knowledge, this is the first AUL in which a balanced t(5;10)(q35;p12) leading to fusion of HNRNPH1 with MLLT10 has been detected. The relative leukemogenic importance of the chimeras and gene losses cannot be reliably assessed, but both mechanisms were probably important in the development of AUL.
背景/目的：急性未分化白血病（AUL）是一种不表达谱系特异性抗原的白血病。此类病例较为罕见，占所有急性白血病的 2.7%。已报道的 AUL 的遗传信息仅限于不到 100 例具有异常核型的病例，以及少数携带嵌合基因或基因突变的病例。我们在此报告一例 AUL 的遗传发现和临床特征。
对一名 31 岁 AUL 患者诊断时的骨髓细胞进行了遗传研究。G 显带核型分析显示存在异常核型：45，X，-Y，t（5；10）（q35;p12），del（12）（p13）[12]/46，XY[5]。阵列比较基因组杂交检测证实了 G 带所见的 del（12）（p13），还检测到来自 1q、17q、Xp 和 Xq 的额外缺失，对应于这五个染色体臂上约 150 个基因的缺失。RNA 测序检测到六个 HNRNPH1::MLLT10 和四个 MLLT10::HNRNPH1 嵌合转录本，随后通过逆转录聚合酶链反应结合 Sanger 测序进一步证实。荧光原位杂交分析显示存在 HNRNPH1::MLLT10 和 MLLT10::HNRNPH1 嵌合基因。
据我们所知，这是首例检测到导致 HNRNPH1 与 MLLT10 融合的平衡 t（5；10）（q35;p12）的 AUL。嵌合体和基因缺失的相对白血病发生重要性不能可靠评估，但这两种机制可能在 AUL 的发生发展中都很重要。
