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Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells

Multiple myeloma (MM) cells are derived from mature B cells based on immunoglobulin heavy chain (IgH) gene analysis. The onset of MM is often caused by a reciprocal chromosomal translocation (cTr) between chr 14 with IgH and chr 11 with CCND1. We propose that mature B cells gain potential to transfo...

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Autores principales: Azami, Yusuke, Tsuyama, Naohiro, Abe, Yu, Sugai-Takahashi, Misaki, Kudo, Ken-ichi, Ota, Akinobu, Sivasundaram, Karnan, Muramatsu, Moe, Shigemura, Tomonari, Sasatani, Megumi, Hashimoto, Yuko, Saji, Shigehira, Kamiya, Kenji, Hanamura, Ichiro, Ikezoe, Takayuki, Onodera, Masafumi, Sakai, Akira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933289/
https://www.ncbi.nlm.nih.gov/pubmed/33664418
http://dx.doi.org/10.1038/s41598-021-84628-5
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author Azami, Yusuke
Tsuyama, Naohiro
Abe, Yu
Sugai-Takahashi, Misaki
Kudo, Ken-ichi
Ota, Akinobu
Sivasundaram, Karnan
Muramatsu, Moe
Shigemura, Tomonari
Sasatani, Megumi
Hashimoto, Yuko
Saji, Shigehira
Kamiya, Kenji
Hanamura, Ichiro
Ikezoe, Takayuki
Onodera, Masafumi
Sakai, Akira
author_facet Azami, Yusuke
Tsuyama, Naohiro
Abe, Yu
Sugai-Takahashi, Misaki
Kudo, Ken-ichi
Ota, Akinobu
Sivasundaram, Karnan
Muramatsu, Moe
Shigemura, Tomonari
Sasatani, Megumi
Hashimoto, Yuko
Saji, Shigehira
Kamiya, Kenji
Hanamura, Ichiro
Ikezoe, Takayuki
Onodera, Masafumi
Sakai, Akira
author_sort Azami, Yusuke
collection PubMed
description Multiple myeloma (MM) cells are derived from mature B cells based on immunoglobulin heavy chain (IgH) gene analysis. The onset of MM is often caused by a reciprocal chromosomal translocation (cTr) between chr 14 with IgH and chr 11 with CCND1. We propose that mature B cells gain potential to transform by reprograming, and then chromosomal aberrations cause the development of abnormal B cells as a myeloma-initiating cell during B cell redifferentiation. To study myeloma-initiating cells, we have already established normal B cell-derived induced pluripotent stem cells (BiPSCs). Here we established two BiPSCs with reciprocal cTr t(11;14) using the CRISPR/Cas9 system; the cleavage site were located in the IgH Eμ region of either the VDJ rearranged allele or non-rearranged allele of IgH and the 5′-upsteam region of the CCND1 (two types of BiPSC13 with t(11;14) and MIB2-6 with t(11;14)). Furthermore, p53 was deleted using the CRISPR/Cas9 system in BiPSC13 with t(11;14). These BiPSCs differentiated into hematopoietic progenitor cells (HPCs). However, unlike cord blood, those HPCs did not differentiated into B lymphocytes by co-culture with BM stromal cell. Therefore, further ingenuity is required to differentiate those BiPSCs-derived HPCs into B lymphocytes.
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spelling pubmed-79332892021-03-08 Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells Azami, Yusuke Tsuyama, Naohiro Abe, Yu Sugai-Takahashi, Misaki Kudo, Ken-ichi Ota, Akinobu Sivasundaram, Karnan Muramatsu, Moe Shigemura, Tomonari Sasatani, Megumi Hashimoto, Yuko Saji, Shigehira Kamiya, Kenji Hanamura, Ichiro Ikezoe, Takayuki Onodera, Masafumi Sakai, Akira Sci Rep Article Multiple myeloma (MM) cells are derived from mature B cells based on immunoglobulin heavy chain (IgH) gene analysis. The onset of MM is often caused by a reciprocal chromosomal translocation (cTr) between chr 14 with IgH and chr 11 with CCND1. We propose that mature B cells gain potential to transform by reprograming, and then chromosomal aberrations cause the development of abnormal B cells as a myeloma-initiating cell during B cell redifferentiation. To study myeloma-initiating cells, we have already established normal B cell-derived induced pluripotent stem cells (BiPSCs). Here we established two BiPSCs with reciprocal cTr t(11;14) using the CRISPR/Cas9 system; the cleavage site were located in the IgH Eμ region of either the VDJ rearranged allele or non-rearranged allele of IgH and the 5′-upsteam region of the CCND1 (two types of BiPSC13 with t(11;14) and MIB2-6 with t(11;14)). Furthermore, p53 was deleted using the CRISPR/Cas9 system in BiPSC13 with t(11;14). These BiPSCs differentiated into hematopoietic progenitor cells (HPCs). However, unlike cord blood, those HPCs did not differentiated into B lymphocytes by co-culture with BM stromal cell. Therefore, further ingenuity is required to differentiate those BiPSCs-derived HPCs into B lymphocytes. Nature Publishing Group UK 2021-03-04 /pmc/articles/PMC7933289/ /pubmed/33664418 http://dx.doi.org/10.1038/s41598-021-84628-5 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Azami, Yusuke
Tsuyama, Naohiro
Abe, Yu
Sugai-Takahashi, Misaki
Kudo, Ken-ichi
Ota, Akinobu
Sivasundaram, Karnan
Muramatsu, Moe
Shigemura, Tomonari
Sasatani, Megumi
Hashimoto, Yuko
Saji, Shigehira
Kamiya, Kenji
Hanamura, Ichiro
Ikezoe, Takayuki
Onodera, Masafumi
Sakai, Akira
Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells
title Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells
title_full Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells
title_fullStr Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells
title_full_unstemmed Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells
title_short Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells
title_sort chromosomal translocation t(11;14) and p53 deletion induced by the crispr/cas9 system in normal b cell-derived ips cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933289/
https://www.ncbi.nlm.nih.gov/pubmed/33664418
http://dx.doi.org/10.1038/s41598-021-84628-5
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