UCL Cancer Institute Seminar Series

Hematopoietic stem cell (HSC) function requires bone marrow niches, which have been proposed to be co-opted by leukemia cells to support their propagation. Using both an experimental model and human bone marrow samples of T-cell acute lymphoblastic leukemia (T-ALL), we documented dramatic remodeling of the osteoblastic lineage, while T-ALL cells appeared to be microenvironment agnostic throughout disease progression. More recently, we have analysed an acute myeloid leukemia (AML) experimental model, in which we uncovered hierarchical vascular remodeling with AML progression. AML cells outcompete non-malignant hematopoiesis by gradual elimination of stroma cells, endosteal endothelium, and osteoblastic cells. While central marrow remains vascularized and splenic vascular niches expand, the remodeled endosteal regions lose the ability to retain HSCs. Overall, the endosteal endothelium microenvironment is altered by AML, yet by preserving it we rescue HSC loss and promote chemotherapeutic efficacy. 

Dr Cristina Lo Selso academic profile

Hosted by: Professor Adele Fielding 

Selected publications: 

Hawkins ED, Duarte D, Akinduro O, Khorshed RA, Passaro D, Nowicka M, Straszkowski L, Scott MK, Rothery S, Foster K, Ruivo N, Waibel M, Johnstone RW, Harrison SJ, Westerman DA, Quach H, Gribben

J, Robinson MD, Purton LE, Bonnet D, Lo Celso C. (2016) T cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments. Nature. 538(7626):518-522. 

Khorshed R, Duarte D, Spitaler M, Scott M, Akinduro O, Rashidi N, Lo Celso C (2015): Automated multi-resolution segmentation allows recognition and multi-parametric quantification of haematopoietic stem cells in their natural bone marrow microenvironment. Stem Cell Reports, 5:139-53.

Rashidi N*, Scott M*, Scherf N, Kalchschmidt J, Roeder I, Selkirk M, Gounaris K, Lo Celso C (2014): In vivo time-lapse imaging shows diverse niche engagement by quiescent and naturally activated haematopoietic stem cells. Blood 124(1):79-83.

Location

UCL Cancer Institute
Courtyard Café
72 Huntley Street
London, WC1E 6DD

Contact: Veronica Dominguez v.dominguez@ucl.ac.uk