Emergence of clone with PHF6 nonsense mutation in chronic myelomonocytic leukemia at relapse after allogeneic HCT

被引:0
|
作者
Yu Akahoshi
Hideki Nakasone
Machiko Kusuda
Kazuaki Kameda
Yuhei Nakamura
Masakatsu Kawamura
Junko Takeshita
Shunto Kawamura
Nozomu Yoshino
Yukiko Misaki
Kazuki Yoshimura
Shimpei Matsumi
Ayumi Gomyo
Aki Tanihara
Masaharu Tamaki
Shun-ichi Kimura
Shinichi Kako
Yoshinobu Kanda
机构
[1] Jichi Medical University Saitama Medical Center,Division of Hematology
来源
International Journal of Hematology | 2022年 / 115卷
关键词
PHF6; Chronic myelomonocytic leukemia; Relapse; Allogeneic hematopoietic cell transplantation; TNF-α signaling pathway;
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学科分类号
摘要
Disease relapse is a major cause of treatment failure after allogeneic hematopoietic cell transplantation (HCT) and the mechanisms of relapse remain unclear. We encountered a 58-year-old man with chronic myelomonocytic leukemia (CMML) that relapsed after haploidentical HCT from his daughter. Peripheral blood samples collected at HCT and at relapse were analyzed, and CD14+/CD16− monocytes that typically accumulate in CMML were isolated by flow cytometry. Whole-exome sequencing of the monocytes revealed 8 common mutations in CMML at HCT. In addition, a PHF6 nonsense mutation not detected at HCT was detected at relapse. RNA sequencing could not detect changes in expression of HLA or immune-checkpoint molecules, which are important mechanisms of immune evasion. However, gene set enrichment analysis (GSEA) revealed that a TNF-α signaling pathway was downregulated at relapse. Ubiquitination of histone H2B at lysine residue 120 (H2BK120ub) at relapse was significantly decreased at the protein level, indicating that PHF6 loss might downregulate a TNF-α signaling pathway by reduction of H2BK120ub. This case illustrates that PHF6 loss contributes to a competitive advantage for the clone under stress conditions and leads to relapse after HCT.
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页码:748 / 752
页数:4
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