Identification of a CD138-Negative Therapy-Resistant Subpopulation in Multiple Myeloma with Vulnerability to Splicing Factor Inhibition
Single-cell RNA sequencing coupled with VDJ-targeted profiling identified distinct therapy-resistant subpopulations within the minor CD138- fraction of multiple myeloma cells. These subpopulations were characterized by increased differential splicing events associated with overexpression of splicing factors from the SR protein family, with CD138- cells showing selective vulnerability to pharmacologic targeting of the splicing factor RBM39. See related commentary by Maron and Abdel-Wahab, p. 535.
Authors
- Shuhei Koide (ORCID: https://orcid.org/0000-0001-8599-6115)
- Taku Kikuchi (ORCID: https://orcid.org/0000-0002-3210-7756)
- Akiho Tsuchiya (ORCID: https://orcid.org/0009-0001-9775-0822)
- Bahityar Rahmutulla (ORCID: https://orcid.org/0000-0002-4014-2789)
- Masayuki Yamashita (ORCID: https://orcid.org/0000-0001-9459-4329)
- Kiyoshi Yamaguchi (ORCID: https://orcid.org/0000-0003-2113-4369)
- Yoichi Furukawa (ORCID: https://orcid.org/0000-0003-0462-8631)
- Naoki Itokawa (ORCID: https://orcid.org/0000-0002-2091-4948)
- Keisuke Kataoka (ORCID: https://orcid.org/0000-0002-8263-9902)
- Atsushi Iwama (ORCID: https://orcid.org/0000-0001-9410-8992)
- Noriko Doki (ORCID: https://orcid.org/0000-0002-8661-3179)
- Ryoji Ito (ORCID: https://orcid.org/0000-0003-2903-2332)
- Shinichiro Okamoto (ORCID: https://orcid.org/0000-0002-6257-4152)
- Kazumasa Aoyama (ORCID: https://orcid.org/0000-0002-2136-4562)
- Takayuki Shimizu (ORCID: https://orcid.org/0009-0008-9177-4760)
- Yaeko Nakajima‐Takagi (ORCID: https://orcid.org/0000-0002-2341-2409)
- Akihide Yoshimi (ORCID: https://orcid.org/0000-0002-0664-7281)
- Takahiro Kamiya (ORCID: https://orcid.org/0000-0003-3080-3747)
- Satoshi Kaito (ORCID: https://orcid.org/0000-0001-7966-291X)
- Atsushi Kaneda (ORCID: https://orcid.org/0000-0002-6980-5515)
- Motohiko Oshima (ORCID: https://orcid.org/0000-0001-6991-815X)
- Masahiko Ajiro (ORCID: https://orcid.org/0000-0002-7079-4788)
- Nobuhiro Tsukada (ORCID: https://orcid.org/0000-0003-2914-2670)
Institutions
- St. Jude Children's Research Hospital (US)
- Chiba University (JP)
- Keio University (JP)
- Central Institute for Experimental Animals (JP)
- Kyoto University (JP)
- Tokyo Metropolitan Komagome Hospital (JP)
- Tokyo Medical Center (JP)
- Chiba University Hospital (JP)
- Japanese Red Cross Medical Center (JP)
- Institute for Advanced Medical Research (US)
- Tokyo National Hospital (JP)
- National Cancer Research Institute (GB)
- The University of Tokyo (JP)
Publication Details
- Journal
- Blood Cancer Discovery
- Published
- 2025-08-29
- DOI
- https://doi.org/10.1158/2643-3230.bcd-24-0340
- Citations
- 1
- Primary Topic
- Multiple Myeloma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.77