慢性淋巴细胞白血病（CLL）中具有立体化B细胞受体免疫球蛋白的染色质激活景观目前尚不清楚。在这里，我们报道了22个CLL的全基因组染色质谱分析结果，这些CLL来自主要亚组，与非立体化的CLL和正常的B细胞亚群进行了比较。尽管第1、2和4个亚组与其非立体化的CLL对应物相差不大，但第8个亚组显示了非常独特的染色质激活谱。特别是，我们在这个亚组中发现了209个新的活性调控元素，这些元素与发生Richter变性的U-CLL具有相似的模式。这些区域富含9个高度表达的转录因子的结合位点。在209个区域中的78个中，我们确定了113个候选的过度表达的靶基因，其中11个区域与超过两个相邻基因相关。这些基因包括7个基因块，表明在同一基因组区域内存在局部共同上调。我们的发现进一步凸显了8号亚组CLL的独特性，这些CLL在所有CLL中的Richter变性风险最高，并提供了进一步的线索，以解析其临床行为的分子基础。版权 ©2023美国血液学会。

The chromatin activation landscape of chronic lymphocytic leukemia (CLL) with stereotyped B-cell receptor immunoglobulin is currently unknown. Here, we report the results of a whole-genome chromatin profiling of histone 3 lysine 27 acetylation of 22 CLLs from major subsets which were compared against non-stereotyped CLLs and normal B cell subpopulations. Although subsets #1, #2, and #4 did not differ much from their non-stereotyped CLL counterparts, subset #8 displayed a remarkably distinct chromatin activation profile. In particular, we identified 209 de novo active regulatory elements in this subset, which showed similar patterns with U-CLLs undergoing Richter transformation. These regions were enriched for binding sites of 9 overexpressed transcription factors. In 78/209 regions, we identified 113 candidate overexpressed target genes, being 11 regions associated with more than two adjacent genes. These included blocks of up to 7 genes, suggesting a local co-upregulation within the same genome compartment. Our findings further underscore the uniqueness of subset #8 CLLs, notable for the highest risk of Richter's transformation amongst all CLL, and provide additional clues to decipher the molecular basis of its clinical behavior.Copyright © 2023 American Society of Hematology.