Our long-term objectives are to understand the genetic pathways that control human hematopoietic stem cells (HSCs) and to determine how changes in these programs lead to generating leukemic stem cells (LSC). By identifying the target pathways involved in these changes, we will be able to contribute to the development of targeted therapeutics.
Tracing the origins of relapse in acute myeloid leukaemia to stem cells. In acute myeloid leukaemia, long-term survival is poor as most patients relapse despite achieving remission. Historically, the failure of therapy has been thought to be due to mutations that produce drug resistance, possibly arising as a consequence of the mutagenic properties of chemotherapy drugs. However, other lines of evidence have pointed to the pre-existence of drug-resistant cells. Full Story can be view in pubmed abstract.
A 17-gene stemness score for rapid determination of risk in acute leukaemia. Refractoriness to induction chemotherapy and relapse after achievement of remission are the main obstacles to cure in acute myeloid leukaemia (AML). After standard induction chemotherapy, patients are assigned to different post-remission strategies on the basis of cytogenetic and molecular abnormalities that broadly define adverse, intermediate and favourable risk categories. However, some patients do not respond to induction therapy and another subset will eventually relapse despite the lack of adverse risk factors. Full Story can be view in pubmed abstract.
miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells. To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Full Story can be view in pubmed abstract.