Frequency of infections in 948 MPN patients: a prospective multicenter patient-reported pilot study

  1. Crodel, Carl C.
  2. Jentsch-Ullrich, Kathleen
  3. Koschmieder, Steffen ORCID logo
  4. Kämpfe, Dietrich
  5. Griesshammer, Martin
  6. Döhner, Konstanze
  7. Jost, Philipp J. ORCID logo
  8. Wolleschak, Denise
  9. Isfort, Susanne
  10. Stegelmann, Frank
  11. Jilg, Stefanie
  12. Hofmann, Verena
  13. Auteri, Guiseppe
  14. Rachow, Tobias
  15. Ernst, Philipp
  16. Brioli, Annamaria ORCID logo
  17. von Lilienfeld-Toal, Marie
  18. Hochhaus, Andreas
  19. PALANDRI, FRANCESCA ORCID logo
  20. Heidel, Florian H.

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1000 Titel
  • Frequency of infections in 948 MPN patients: a prospective multicenter patient-reported pilot study
1000 Autor/in
  1. Crodel, Carl C. |
  2. Jentsch-Ullrich, Kathleen |
  3. Koschmieder, Steffen |
  4. Kämpfe, Dietrich |
  5. Griesshammer, Martin |
  6. Döhner, Konstanze |
  7. Jost, Philipp J. |
  8. Wolleschak, Denise |
  9. Isfort, Susanne |
  10. Stegelmann, Frank |
  11. Jilg, Stefanie |
  12. Hofmann, Verena |
  13. Auteri, Guiseppe |
  14. Rachow, Tobias |
  15. Ernst, Philipp |
  16. Brioli, Annamaria |
  17. von Lilienfeld-Toal, Marie |
  18. Hochhaus, Andreas |
  19. PALANDRI, FRANCESCA |
  20. Heidel, Florian H. |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-05-30
1000 Erschienen in
1000 Quellenangabe
  • 34(7):1949-1953
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41375-020-0890-1 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261209/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Drug combinations that target critical pathways are a mainstay of cancer care. To improve current approaches to combination treatment of chronic lymphocytic leukemia (CLL) and gain insights into the underlying biology, we studied the effect of 352 drug combination pairs in multiple concentrations by analysing ex vivo drug response of 52 primary CLL samples, which were characterized by 'omics' profiling. Known synergistic interactions were confirmed for B-cell receptor (BCR) inhibitors with Bcl-2 inhibitors and with chemotherapeutic drugs, suggesting that this approach can identify clinically useful combinations. Moreover, we uncovered synergistic interactions between BCR inhibitors and afatinib, which we attribute to BCR activation by afatinib through BLK upstream of BTK and PI3K. Combinations of multiple inhibitors of BCR components (e.g., BTK, PI3K, SYK) had effects similar to the single agents. While PI3K and BTK inhibitors produced overall similar effects in combinations with other drugs, we uncovered a larger response heterogeneity of combinations including PI3K inhibitors, predominantly in CLL with mutated IGHV, which we attribute to the target's position within the BCR-signaling pathway. Taken together, our study shows that drug combination effects can be effectively queried in primary cancer cells, which could aid discovery, triage and clinical development of drug combinations.
1000 Sacherschließung
lokal Surveys and Questionnaires [MeSH]
lokal Adolescent [MeSH]
lokal Female [MeSH]
lokal Letter
lokal Follow-Up Studies [MeSH]
lokal Aged, 80 and over [MeSH]
lokal Aged [MeSH]
lokal Adult [MeSH]
lokal Sickness Impact Profile [MeSH]
lokal Humans [MeSH]
lokal Prospective Studies [MeSH]
lokal Severity of Illness Index [MeSH]
lokal Middle Aged [MeSH]
lokal Infections/diagnosis [MeSH]
lokal Risk factors
lokal Patient Reported Outcome Measures [MeSH]
lokal Myeloproliferative disease
lokal Male [MeSH]
lokal Myeloproliferative Disorders/complications [MeSH]
lokal Quality of Life [MeSH]
lokal Pilot Projects [MeSH]
lokal Prognosis [MeSH]
lokal Young Adult [MeSH]
lokal Infections/etiology [MeSH]
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/Q3JvZGVsLCBDYXJsIEMu|https://frl.publisso.de/adhoc/uri/SmVudHNjaC1VbGxyaWNoLCBLYXRobGVlbg==|https://orcid.org/0000-0002-1011-8171|https://frl.publisso.de/adhoc/uri/S8OkbXBmZSwgRGlldHJpY2g=|https://frl.publisso.de/adhoc/uri/R3JpZXNzaGFtbWVyLCBNYXJ0aW4=|https://frl.publisso.de/adhoc/uri/RMO2aG5lciwgS29uc3Rhbnpl|https://orcid.org/0000-0003-2454-0362|https://frl.publisso.de/adhoc/uri/V29sbGVzY2hhaywgRGVuaXNl|https://frl.publisso.de/adhoc/uri/SXNmb3J0LCBTdXNhbm5l|https://frl.publisso.de/adhoc/uri/U3RlZ2VsbWFubiwgRnJhbms=|https://frl.publisso.de/adhoc/uri/SmlsZywgU3RlZmFuaWU=|https://frl.publisso.de/adhoc/uri/SG9mbWFubiwgVmVyZW5h|https://frl.publisso.de/adhoc/uri/QXV0ZXJpLCBHdWlzZXBwZQ==|https://frl.publisso.de/adhoc/uri/UmFjaG93LCBUb2JpYXM=|https://frl.publisso.de/adhoc/uri/RXJuc3QsIFBoaWxpcHA=|https://orcid.org/0000-0002-4072-7592|https://frl.publisso.de/adhoc/uri/dm9uIExpbGllbmZlbGQtVG9hbCwgTWFyaWU=|https://frl.publisso.de/adhoc/uri/SG9jaGhhdXMsIEFuZHJlYXM=|https://orcid.org/0000-0001-8367-5668|https://frl.publisso.de/adhoc/uri/SGVpZGVsLCBGbG9yaWFuIEgu
1000 Hinweis
  • DeepGreen-ID: 729197078dd048d384513f5a815e79b5 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
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1000 Erstellt am 2023-11-18T10:33:22.296+0100
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1000 Zuletzt bearbeitet Wed Apr 10 11:57:40 CEST 2024
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