Long-term in vitro maintenance of clonal abundance and leukaemia-initiating potential in acute lymphoblastic leukaemia

摘要: Lack of suitable in vitro culture conditions for primary acute lymphoblastic leukaemia (ALL) cells severely impairs their experimental accessibility and the testing new drugs on cell material reflecting clonal heterogeneity patients. We show that Nestin-positive human mesenchymal stem (MSCs) support expansion a range biologically clinically distinct patient-derived ALL samples. Adherent showed an increased accumulation S phase cycle diminished apoptosis when compared with suspension fraction. Moreover, surface expression adhesion molecules CD34, CDH2 CD10 several fold. Approximately 20% were G0 cycle, suggesting MSCs may quiescent cells. Cellular barcoding demonstrated long-term preservation abundance. Expansion >3 months compromised neither feeder dependence nor cancer initiating ability as judged by engraftment potential immunocompromised mice. Finally, we demonstrate suitability this co-culture approach investigation drug combinations luciferase-expressing primograft Taken together, have developed preclinical platform will facilitate development effective combination therapies ALL.