Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


          Institute: MPI für Evolutionsbiologie     Collection: Research Group Evolutionary Theory     Display Documents



  history
ID: 564940.0, MPI für Evolutionsbiologie / Research Group Evolutionary Theory
Explaining the in vitro and in vivo differences in leukemia therapy
Authors:Lenaerts, Tom; Castagnetti, Fausto; Traulsen, Arne; Pacheco, Jorge M.; Rosti, Gianantonio; Dingli, David
Language:English
Date of Publication (YYYY-MM-DD):2011-05-15
Title of Journal:Cell Cycle
Volume:10
Issue / Number:10
Start Page:1540
End Page:1544
Review Status:not specified
Audience:Not Specified
Abstract / Description:The majority of patients with chronic myeloid leukemia in early chronic phase (CML-ECP) who are treated with imatinib achieve a complete cytogenetic response with a significant reduction in the risk of progression to advanced phases. Recent studies show that therapy of CML-ECP with nilotinib leads to a faster and deeper response compared to imatinib. However, in vitro data indicates that there is no detectable difference in inhibition of signaling downstream of Bcr-Abl between the two agents and that neither drug induces apoptosis of CML CD34(+) cells. We use a computational model of hematopoiesis and CML, combined with serial quantitative data of disease burden under imatinib and nilotinib therapy to explain this apparent disconnect between in vivo and in vitro responses. We show how a subtle difference in the differentiation rate of CML cells under therapy with either agent, with marginal impact onto the in vitro studies, translates into a significantly different reproductive fitness of treated cells in vivo, providing a sizeable difference, hence providing an explanation for the superior response observed with nilotinib.
Free Keywords:hematopoiesis; self-renewal; selection; evolution; reproductive fitness
External Publication Status:published
Document Type:Article
Communicated by:Brigitte Lechner
Affiliations:MPI für Evolutionsbiologie/AG Evolutionstheorie
External Affiliations:Mayo Clin, Coll Med, Div Hematol, Rochester, MN 55905 USA;
Univ Libre Bruxelles, Dept Informat, Machine Learning Grp, Brussels, Belgium; Vrije Univ Brussel, Dept Comp Sci, A1 Lab, Brussels, Belgium; L & A Seragnoli St Orsola Univ Hosp, Dept Hematol & Oncol, Bologna, Italy; Univ Minho, Dept Matemat Aplicacoes, Braga, Portugal; Ctr Matemat & Aplicacoes Fundamentais, ATP Grp, Lisbon, Portugal
Identifiers:ISSN:1538-4101 (print) [ID-No:1]
ISSN:1551-4005 (online) [ID-No:2]
DOI:10.4161/cc.10.10.15518 [ID-No:3]
LOCALID:2839/S 39182 [Listen-Nummer/S-Nummer]
Full Text:
Sorry, no privileges
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.