The production of blood cells, hematopoiesis, is maintained by a small number of hematopoietic stem cells (HSCs) that have the capacity to differentiate into all hematopoietic lineages, and at the same time self-renew to maintain the HSC pool. These properties make HSCs essential for maintaining hematopoietic homeostasis and for reconstitution of patients during treatment of hematological disorders and malignant diseases.
Similarly to normal hematopoiesis, leukemias are organized in cellular hierarchies where leukemic stem cells (LSCs) drive the tumor growth. LSCs have stem cell characteristics such as self-renewal capacity, quiescence and drug resistance, causing metastasis and relapse. LSCs are therefore a critical priority as targets for therapy.
The objective of our research is to molecularly dissect known stem cell populations in order to discriminate between normal and malignant stem cells. This will allow for defining the transcriptional programs that govern HSC fate and explain the molecular basis for leukemogenesis. Ultimately we will use this information to therapeutically target LSCs and thereby improve the treatment of leukemia.