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Hematopoietic stem progenitor cells with malignancy‐related gene mutations in patients with acquired aplastic anemia are characterized by the increased expression of CXCR4
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 suppo...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9422028/ https://www.ncbi.nlm.nih.gov/pubmed/36051022 http://dx.doi.org/10.1002/jha2.515 |
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author | 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 |
author_facet | 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 |
author_sort | Katagiri, Takamasa |
collection | PubMed |
description | 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 (n = 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 (c‐kit, t[8;21], monosomy 7 [one for each], ASXL1 [n = 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. |
format | Online Article Text |
id | pubmed-9422028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94220282022-08-31 Hematopoietic stem progenitor cells with malignancy‐related gene mutations in patients with acquired aplastic anemia are characterized by the increased expression of CXCR4 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 EJHaem Sickle Cell, Thrombosis, and Benign Haematology 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 (n = 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 (c‐kit, t[8;21], monosomy 7 [one for each], ASXL1 [n = 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. John Wiley and Sons Inc. 2022-07-03 /pmc/articles/PMC9422028/ /pubmed/36051022 http://dx.doi.org/10.1002/jha2.515 Text en © 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Sickle Cell, Thrombosis, and Benign Haematology 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 Hematopoietic stem progenitor cells with malignancy‐related gene mutations in patients with acquired aplastic anemia are characterized by the increased expression of CXCR4 |
title | Hematopoietic stem progenitor cells with malignancy‐related gene mutations in patients with acquired aplastic anemia are characterized by the increased expression of CXCR4 |
title_full | Hematopoietic stem progenitor cells with malignancy‐related gene mutations in patients with acquired aplastic anemia are characterized by the increased expression of CXCR4 |
title_fullStr | Hematopoietic stem progenitor cells with malignancy‐related gene mutations in patients with acquired aplastic anemia are characterized by the increased expression of CXCR4 |
title_full_unstemmed | Hematopoietic stem progenitor cells with malignancy‐related gene mutations in patients with acquired aplastic anemia are characterized by the increased expression of CXCR4 |
title_short | Hematopoietic stem progenitor cells with malignancy‐related gene mutations in patients with acquired aplastic anemia are characterized by the increased expression of CXCR4 |
title_sort | hematopoietic stem progenitor cells with malignancy‐related gene mutations in patients with acquired aplastic anemia are characterized by the increased expression of cxcr4 |
topic | Sickle Cell, Thrombosis, and Benign Haematology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9422028/ https://www.ncbi.nlm.nih.gov/pubmed/36051022 http://dx.doi.org/10.1002/jha2.515 |
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