The ecology in the hematopoietic stem cell niche determines the clinical outcome in chronic myeloid leukemia

• DOI: 10.1073/pnas.1317072111
• Publication Date: 2014-02-25T02:44:15Z
• Authors: Adam L. MacLean; Sarah Filippi; Michael P. H. Stumpf
• Keywords: Hematopoietic stem cell

Chronic myeloid leukemia (CML) is a blood disease that disrupts normal function of the hematopoietic system. Despite great progress made in terms molecular therapies for CML, there remain large gaps our understanding. By comparing mathematical models describe CML progression and etiology we sought to identify those provide best description dynamics their underlying mechanisms. Data two clinical outcomes--disease remission or relapse--are considered, investigate these using Bayesian inference techniques throughout. We find it not possible choose between based on fits data alone; however, by studying model predictions can discard fail take niche effects into account. More detailed analysis remaining reveals mechanistic differences: one model, stem cell determine outcome; other determined at stage progenitor cells, particular differences death rates. This also distinct transient will be experimentally accessible, but are currently limits what measure. To resolve need able probe directly. Our highlights importance further mapping bone marrow microenvironment as "ecological" interactions cells this appear intricately linked outcome.