Combined population dynamics and entropy modelling supports patient stratification in chronic myeloid leukemia

Brehme, M., Koschmieder, S., Montazeri, M., Copland, M. , Oehler, V. G., Radich, J. P., Brümmendorf, T. H., and Schuppert, A. (2016) Combined population dynamics and entropy modelling supports patient stratification in chronic myeloid leukemia. Scientific Reports, 6, 24057. (doi:10.1038/srep24057) (PMID:27048866) (PMCID:PMC4822142)

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Abstract

Modelling the parameters of multistep carcinogenesis is key for a better understanding of cancer progression, biomarker identification and the design of individualized therapies. Using chronic myeloid leukemia (CML) as a paradigm for hierarchical disease evolution we show that combined population dynamic modelling and CML patient biopsy genomic analysis enables patient stratification at unprecedented resolution. Linking CD34+ similarity as a disease progression marker to patientderived gene expression entropy separated established CML progression stages and uncovered additional heterogeneity within disease stages. Importantly, our patient data informed model enables quantitative approximation of individual patients’ disease history within chronic phase (CP) and significantly separates “early” from “late” CP. Our findings provide a novel rationale for personalized and genome-informed disease progression risk assessment that is independent and complementary to conventional measures of CML disease burden and prognosis.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Copland, Professor Mhairi
Authors: Brehme, M., Koschmieder, S., Montazeri, M., Copland, M., Oehler, V. G., Radich, J. P., Brümmendorf, T. H.,, and Schuppert, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN:2045-2322
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Scientific Reports 6:24057
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
506532An investigation of the control of cell division and quiescence in leukaemic versus normal haemopoietic stem and progenitor cellsMhairi CoplandBloodwise (BLOODWIS)11017RI CANCER SCIENCES
506531An investigation of the control of cell division and quiescence in leukaemic versus normal haemopoietic stem and progenitor cellsMhairi CoplandScottish Executive Health Department (SEHHD-CSO)SCD/04RI CANCER SCIENCES