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

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
Date of Publication (YYYY-MM-DD):2011-05-15
Title of Journal:Cell Cycle
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]
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