Katagiri Takamasa, Espinoza Jorge Luis, Uemori Mizuho, Ikeda Honoka, Hosokawa Kohei, Ishiyama Ken, Yoroidaka Takeshi, Imi Tatsuya, Takamatsu Hiroyuki, Ozawa Tatsuhiko, Kishi Hiroyuki, Yamamoto Yasuhiko, Elbadry Mahmoud Ibrahim, Yoshida Yoshinori, Chonabayashi Kazuhisa, Takenaka Katsuto, Akashi Koichi, Nannya Yasuhito, Ogawa Seishi, Nakao Shinji
Department of Clinical Laboratory Science Graduate School of Medical Science Institute of Medical Pharmaceutical and Health Sciences Kanazawa University Kanazawa Ishikawa Japan.
Department of Occupational Therapy Graduate School of Medical Science Institute of Medical Pharmaceutical and Health Sciences Kanazawa University Kanazawa Ishikawa Japan.
EJHaem. 2022 Jul 3;3(3):669-680. doi: 10.1002/jha2.515. eCollection 2022 Aug.
The phenotypic changes in hematopoietic stem progenitor cells (HSPCs) with somatic mutations of malignancy-related genes in patients with acquired aplastic anemia (AA) are poorly understood. As our initial study showed increased CXCR4 expression on HLA allele-lacking (HLA[-]) HSPCs that solely support hematopoiesis in comparison to redundant HLA(+) HSPCs in AA patients, we screened the HSPCs of patients with various types of bone marrow (BM) failure to investigate their CXCR4 expression. In comparison to healthy individuals ( = 15, 12.3%-49.9%, median 43.2%), the median CXCR4 cell percentages in the HSPCs of patients without somatic mutations were low: 29.3% (14.3%-37.3%) in the eight patients without HLA(-) granulocytes, 8.8% (4.1%-9.8%) in the five patients with HLA(-) cells accounting for >90% of granulocytes, and 7.8 (2.1%-8.7%) in the six patients with paroxysmal nocturnal hemoglobinuria. In contrast, the median percentage was much higher (78% [61.4%-88.7%]) in the five AA patients without HLA(-) granulocytes possessing somatic mutations (, t[8;21], monosomy 7 [one for each], [ = 2]), findings that were comparable to those (66.5%, 63.1%-88.9%) in the four patients with advanced myelodysplastic syndromes. The increased expression of CXCR4 may therefore reflect intrinsic abnormalities of HSPCs caused by somatic mutations that allow them to evade restriction by BM stromal cells.
对于获得性再生障碍性贫血（AA）患者中具有恶性肿瘤相关基因体细胞突变的造血干祖细胞（HSPCs）的表型变化，人们了解甚少。正如我们的初步研究表明，与AA患者中多余的HLA(+) HSPCs相比，仅支持造血的缺乏HLA等位基因（HLA[-]）的HSPCs上CXCR4表达增加，我们筛选了各种类型骨髓（BM）衰竭患者的HSPCs，以研究其CXCR4表达。与健康个体相比（n = 15，12.3%-49.9%，中位数43.2%），没有体细胞突变的患者的HSPCs中CXCR4细胞百分比中位数较低：8例无HLA(-)粒细胞的患者中为29.3%（14.3%-37.3%），5例HLA(-)细胞占粒细胞>90%的患者中为8.8%（4.1%-9.8%），6例阵发性夜间血红蛋白尿患者中为7.8（2.1%-8.7%）。相比之下，5例没有HLA(-)粒细胞但具有体细胞突变的AA患者中，中位数百分比要高得多（78% [61.4%-88.7%]）（n，t[8;21]，7号染色体单体[各1例]，n [n = 2]），这一结果与4例晚期骨髓增生异常综合征患者（66.5%，63.1%-88.9%）的结果相当。因此，CXCR4表达增加可能反映了由体细胞突变引起的HSPCs内在异常，使它们能够逃避骨髓基质细胞的限制。
