Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis
Intratumor heterogeneity as a clinical challenge becomes most evident after several treatment lines, when multidrug-resistant subclones accumulate. To address this challenge, the characterization of resistance mechanisms at the subclonal level is key to identify common vulnerabilities. In this study...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
9 November 2023
|
| In: |
Blood
Year: 2023, Volume: 142, Issue: 19, Pages: 1633-1646 |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood.2023019758 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood.2023019758 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0006497123015562 
|
| Author Notes: | Alexandra M. Poos, Nina Prokoph, Moritz J. Przybilla, Jan-Philipp Mallm, Simon Steiger, Isabelle Seufert, Lukas John, Stephan M. Tirier, Katharina Bauer, Anja Baumann, Jennifer Rohleder, Umair Munawar, Leo Rasche, K. Martin Kortüm, Nicola Giesen, Philipp Reichert, Stefanie Huhn, Carsten Müller-Tidow, Hartmut Goldschmidt, Oliver Stegle, Marc S. Raab, Karsten Rippe, Niels Weinhold |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1871274869 | ||
| 003 | DE-627 | ||
| 005 | 20240307040303.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231127s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1182/blood.2023019758 |2 doi | |
| 035 | |a (DE-627)1871274869 | ||
| 035 | |a (DE-599)KXP1871274869 | ||
| 035 | |a (OCoLC)1425208438 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Poos, Alexandra |d 1988- |e VerfasserIn |0 (DE-588)1178400417 |0 (DE-627)1049344812 |0 (DE-576)517770393 |4 aut | |
| 245 | 1 | 0 | |a Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis |c Alexandra M. Poos, Nina Prokoph, Moritz J. Przybilla, Jan-Philipp Mallm, Simon Steiger, Isabelle Seufert, Lukas John, Stephan M. Tirier, Katharina Bauer, Anja Baumann, Jennifer Rohleder, Umair Munawar, Leo Rasche, K. Martin Kortüm, Nicola Giesen, Philipp Reichert, Stefanie Huhn, Carsten Müller-Tidow, Hartmut Goldschmidt, Oliver Stegle, Marc S. Raab, Karsten Rippe, Niels Weinhold |
| 264 | 1 | |c 9 November 2023 | |
| 300 | |a 14 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 27.11.2023 | ||
| 520 | |a Intratumor heterogeneity as a clinical challenge becomes most evident after several treatment lines, when multidrug-resistant subclones accumulate. To address this challenge, the characterization of resistance mechanisms at the subclonal level is key to identify common vulnerabilities. In this study, we integrate whole-genome sequencing, single-cell (sc) transcriptomics (scRNA sequencing), and chromatin accessibility (scATAC sequencing) together with mitochondrial DNA mutations to define subclonal architecture and evolution for longitudinal samples from 15 patients with relapsed or refractory multiple myeloma. We assess transcriptomic and epigenomic changes to resolve the multifactorial nature of therapy resistance and relate it to the parallel occurrence of different mechanisms: (1) preexisting epigenetic profiles of subclones associated with survival advantages, (2) converging phenotypic adaptation of genetically distinct subclones, and (3) subclone-specific interactions of myeloma and bone marrow microenvironment cells. Our study showcases how an integrative multiomics analysis can be applied to track and characterize distinct multidrug-resistant subclones over time for the identification of molecular targets against them. | ||
| 700 | 1 | |a Prokoph, Nina |e VerfasserIn |0 (DE-588)1311290478 |0 (DE-627)187127642X |4 aut | |
| 700 | 1 | |a Przybilla, Moritz Jakob |e VerfasserIn |0 (DE-588)1218170379 |0 (DE-627)1733587810 |4 aut | |
| 700 | 1 | |a Mallm, Jan-Philipp |e VerfasserIn |0 (DE-588)1029962413 |0 (DE-627)734535619 |0 (DE-576)377783358 |4 aut | |
| 700 | 1 | |a Steiger, Simon |e VerfasserIn |0 (DE-588)1200436075 |0 (DE-627)1683525086 |4 aut | |
| 700 | 1 | |a Seufert, Isabelle |d 1995- |e VerfasserIn |0 (DE-588)1309817898 |0 (DE-627)1870214544 |4 aut | |
| 700 | 1 | |a John, Lukas |e VerfasserIn |0 (DE-588)1161433961 |0 (DE-627)1024730484 |0 (DE-576)506519759 |4 aut | |
| 700 | 1 | |a Tirier, Stephan Marius |e VerfasserIn |0 (DE-588)1175539120 |0 (DE-627)1046550446 |0 (DE-576)516303600 |4 aut | |
| 700 | 1 | |a Bauer, Katharina |e VerfasserIn |0 (DE-588)1207352233 |0 (DE-627)1693629429 |4 aut | |
| 700 | 1 | |a Baumann, Anja |e VerfasserIn |0 (DE-588)1240798776 |0 (DE-627)1769711376 |4 aut | |
| 700 | 1 | |a Rohleder, Jennifer |e VerfasserIn |4 aut | |
| 700 | 1 | |a Munawar, Umair |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rasche, Leo |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kortüm, K. Martin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Giesen, Nicola |d 1983- |e VerfasserIn |0 (DE-588)141844272 |0 (DE-627)631828524 |0 (DE-576)32643657X |4 aut | |
| 700 | 1 | |a Reichert, Philipp |d 1987- |e VerfasserIn |0 (DE-588)1224419979 |0 (DE-627)1743773331 |4 aut | |
| 700 | 1 | |a Huhn, Stefanie |d 1982- |e VerfasserIn |0 (DE-588)1014984424 |0 (DE-627)705313190 |0 (DE-576)349876436 |4 aut | |
| 700 | 1 | |a Müller-Tidow, Carsten |d 1968- |e VerfasserIn |0 (DE-588)1015101798 |0 (DE-627)705330230 |0 (DE-576)351197893 |4 aut | |
| 700 | 1 | |a Goldschmidt, Hartmut |d 1956- |e VerfasserIn |0 (DE-588)102258023X |0 (DE-627)717003809 |0 (DE-576)365637386 |4 aut | |
| 700 | 1 | |a Stegle, Oliver |e VerfasserIn |0 (DE-588)1198235063 |0 (DE-627)1680553755 |4 aut | |
| 700 | 1 | |a Raab, Marc-Steffen |d 1973- |e VerfasserIn |0 (DE-588)124052460 |0 (DE-627)706520998 |0 (DE-576)293998027 |4 aut | |
| 700 | 1 | |a Rippe, Karsten |e VerfasserIn |0 (DE-588)102853261X |0 (DE-627)730885070 |0 (DE-576)168897989 |4 aut | |
| 700 | 1 | |a Weinhold, Niels |e VerfasserIn |0 (DE-588)141225688 |0 (DE-627)626149576 |0 (DE-576)322607388 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Blood |d Washington, DC : American Society of Hematology, 1946 |g 142(2023), 19, Seite 1633-1646 |h Online-Ressource |w (DE-627)266886647 |w (DE-600)1468538-3 |w (DE-576)075961938 |x 1528-0020 |7 nnas |a Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis |
| 773 | 1 | 8 | |g volume:142 |g year:2023 |g number:19 |g pages:1633-1646 |g extent:14 |a Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis |
| 856 | 4 | 0 | |u https://doi.org/10.1182/blood.2023019758 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.sciencedirect.com/science/article/pii/S0006497123015562 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20231127 | ||
| 993 | |a Article | ||
| 994 | |a 2023 | ||
| 998 | |g 141225688 |a Weinhold, Niels |m 141225688:Weinhold, Niels |d 910000 |d 910100 |e 910000PW141225688 |e 910100PW141225688 |k 0/910000/ |k 1/910000/910100/ |p 23 |y j | ||
| 998 | |g 102853261X |a Rippe, Karsten |m 102853261X:Rippe, Karsten |d 700000 |d 716000 |d 140000 |e 700000PR102853261X |e 716000PR102853261X |e 140000PR102853261X |k 0/700000/ |k 1/700000/716000/ |k 0/140000/ |p 22 | ||
| 998 | |g 124052460 |a Raab, Marc-Steffen |m 124052460:Raab, Marc-Steffen |d 910000 |d 910100 |e 910000PR124052460 |e 910100PR124052460 |k 0/910000/ |k 1/910000/910100/ |p 21 | ||
| 998 | |g 1198235063 |a Stegle, Oliver |m 1198235063:Stegle, Oliver |d 140000 |e 140000PS1198235063 |k 0/140000/ |p 20 | ||
| 998 | |g 102258023X |a Goldschmidt, Hartmut |m 102258023X:Goldschmidt, Hartmut |d 50000 |d 910000 |d 910100 |e 50000PG102258023X |e 910000PG102258023X |e 910100PG102258023X |k 0/50000/ |k 0/910000/ |k 1/910000/910100/ |p 19 | ||
| 998 | |g 1015101798 |a Müller-Tidow, Carsten |m 1015101798:Müller-Tidow, Carsten |d 910000 |d 910100 |d 50000 |e 910000PM1015101798 |e 910100PM1015101798 |e 50000PM1015101798 |k 0/910000/ |k 1/910000/910100/ |k 0/50000/ |p 18 | ||
| 998 | |g 1014984424 |a Huhn, Stefanie |m 1014984424:Huhn, Stefanie |d 910000 |d 910100 |e 910000PH1014984424 |e 910100PH1014984424 |k 0/910000/ |k 1/910000/910100/ |p 17 | ||
| 998 | |g 1224419979 |a Reichert, Philipp |m 1224419979:Reichert, Philipp |d 910000 |d 910100 |e 910000PR1224419979 |e 910100PR1224419979 |k 0/910000/ |k 1/910000/910100/ |p 16 | ||
| 998 | |g 1207352233 |a Bauer, Katharina |m 1207352233:Bauer, Katharina |p 9 | ||
| 998 | |g 1175539120 |a Tirier, Stephan Marius |m 1175539120:Tirier, Stephan Marius |p 8 | ||
| 998 | |g 1161433961 |a John, Lukas |m 1161433961:John, Lukas |d 910000 |d 910100 |e 910000PJ1161433961 |e 910100PJ1161433961 |k 0/910000/ |k 1/910000/910100/ |p 7 | ||
| 998 | |g 1309817898 |a Seufert, Isabelle |m 1309817898:Seufert, Isabelle |p 6 | ||
| 998 | |g 1200436075 |a Steiger, Simon |m 1200436075:Steiger, Simon |p 5 | ||
| 998 | |g 1029962413 |a Mallm, Jan-Philipp |m 1029962413:Mallm, Jan-Philipp |d 700000 |d 716000 |e 700000PM1029962413 |e 716000PM1029962413 |k 0/700000/ |k 1/700000/716000/ |p 4 | ||
| 998 | |g 1311290478 |a Prokoph, Nina |m 1311290478:Prokoph, Nina |d 910000 |d 910100 |e 910000PP1311290478 |e 910100PP1311290478 |k 0/910000/ |k 1/910000/910100/ |p 2 | ||
| 998 | |g 1178400417 |a Poos, Alexandra |m 1178400417:Poos, Alexandra |d 910000 |d 910100 |e 910000PP1178400417 |e 910100PP1178400417 |k 0/910000/ |k 1/910000/910100/ |p 1 |x j | ||
| 999 | |a KXP-PPN1871274869 |e 4418488588 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"id":{"eki":["1871274869"],"doi":["10.1182/blood.2023019758"]},"name":{"displayForm":["Alexandra M. Poos, Nina Prokoph, Moritz J. Przybilla, Jan-Philipp Mallm, Simon Steiger, Isabelle Seufert, Lukas John, Stephan M. Tirier, Katharina Bauer, Anja Baumann, Jennifer Rohleder, Umair Munawar, Leo Rasche, K. Martin Kortüm, Nicola Giesen, Philipp Reichert, Stefanie Huhn, Carsten Müller-Tidow, Hartmut Goldschmidt, Oliver Stegle, Marc S. Raab, Karsten Rippe, Niels Weinhold"]},"note":["Gesehen am 27.11.2023"],"type":{"bibl":"article-journal","media":"Online-Ressource"},"language":["eng"],"title":[{"title":"Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis","title_sort":"Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis"}],"relHost":[{"corporate":[{"role":"isb","display":"American Society of Hematology"}],"pubHistory":["1.1946 -"],"titleAlt":[{"title":"Blood online"}],"part":{"volume":"142","year":"2023","text":"142(2023), 19, Seite 1633-1646","extent":"14","issue":"19","pages":"1633-1646"},"id":{"eki":["266886647"],"issn":["1528-0020"],"zdb":["1468538-3"]},"origin":[{"publisherPlace":"Washington, DC ; Philadelphia, Pa. ; Stanford, Calif.","dateIssuedKey":"1946","dateIssuedDisp":"1946-","publisher":"American Society of Hematology ; Saunders ; HighWire Press"}],"note":["Gesehen am 21.04.2023"],"language":["eng"],"type":{"media":"Online-Ressource","bibl":"periodical"},"title":[{"subtitle":"journal of the American Society of Hematology","title_sort":"Blood","title":"Blood"}],"physDesc":[{"extent":"Online-Ressource"}],"recId":"266886647","disp":"Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysisBlood"}],"person":[{"family":"Poos","role":"aut","given":"Alexandra","display":"Poos, Alexandra"},{"display":"Prokoph, Nina","role":"aut","given":"Nina","family":"Prokoph"},{"display":"Przybilla, Moritz Jakob","family":"Przybilla","role":"aut","given":"Moritz Jakob"},{"display":"Mallm, Jan-Philipp","given":"Jan-Philipp","role":"aut","family":"Mallm"},{"display":"Steiger, Simon","family":"Steiger","given":"Simon","role":"aut"},{"display":"Seufert, Isabelle","family":"Seufert","given":"Isabelle","role":"aut"},{"given":"Lukas","role":"aut","family":"John","display":"John, Lukas"},{"display":"Tirier, Stephan Marius","role":"aut","given":"Stephan Marius","family":"Tirier"},{"family":"Bauer","role":"aut","given":"Katharina","display":"Bauer, Katharina"},{"family":"Baumann","role":"aut","given":"Anja","display":"Baumann, Anja"},{"display":"Rohleder, Jennifer","family":"Rohleder","role":"aut","given":"Jennifer"},{"family":"Munawar","role":"aut","given":"Umair","display":"Munawar, Umair"},{"family":"Rasche","given":"Leo","role":"aut","display":"Rasche, Leo"},{"display":"Kortüm, K. Martin","given":"K. Martin","role":"aut","family":"Kortüm"},{"display":"Giesen, Nicola","family":"Giesen","given":"Nicola","role":"aut"},{"display":"Reichert, Philipp","family":"Reichert","role":"aut","given":"Philipp"},{"display":"Huhn, Stefanie","given":"Stefanie","role":"aut","family":"Huhn"},{"display":"Müller-Tidow, Carsten","family":"Müller-Tidow","given":"Carsten","role":"aut"},{"role":"aut","given":"Hartmut","family":"Goldschmidt","display":"Goldschmidt, Hartmut"},{"display":"Stegle, Oliver","family":"Stegle","role":"aut","given":"Oliver"},{"display":"Raab, Marc-Steffen","family":"Raab","role":"aut","given":"Marc-Steffen"},{"family":"Rippe","role":"aut","given":"Karsten","display":"Rippe, Karsten"},{"display":"Weinhold, Niels","given":"Niels","role":"aut","family":"Weinhold"}],"origin":[{"dateIssuedDisp":"9 November 2023","dateIssuedKey":"2023"}],"physDesc":[{"extent":"14 S."}],"recId":"1871274869"} | ||
| SRT | |a POOSALEXANRESOLVINGT9202 | ||