Stem Cells and Leukemia
G. Karlsson group
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.
- Delineate the heterogeneity of human hematopietic stem cell (HSC) populations at different ontogenetic stages and identify novel markers for improved HSC isolation.
- Define leukemic stem cell (LSCs) and identify therapy-insensitive cells in chronic myeloid leukemia (CML).
- Investigate the role for super-enhancers in defining LSC heterogeneity and their potential as therapeutic targets for LSCs.
Leukemia treatment is vulnerable to cellular heterogeneity as rare LSCs often evade therapy and cause relapse. Prospective isolation of human HSCs is in its infancy and current views of the molecular ground state driving HSCs and how it is altered in leukemia is based on studies of heterogeneous populations where HSC and LSC molecular signatures are masked by contaminating cells. Our research aims to define and prospectively isolate treatment-insensitive LSC subpopulations with relevance for therapy response as well to identify prognostic biomarkers for treatment-free remission.
(name linked to profile in Lund University research portal)
Principal Investigator, Goran [dot] Karlsson [at] med [dot] lu [dot] se
Postdoc, Ram_Krishna [dot] Thakur [at] med [dot] lu [dot] se
PhD student, Parashar [dot] Dhapola [at] med [dot] lu [dot] se
PhD student, Fatemeh [dot] Safi [at] med [dot] lu [dot] se
PhD student, Rebecca [dot] Warfvinge [at] med [dot] lu [dot] se
Research Engineer, Linda [dot] Geironson_Ulfsson [at] med [dot] lu [dot] se
Bioinformatician, Rasmus [dot] Olofzon [at] med [dot] lu [dot] se
PhD, Associate Professor
Division of Molecular Hematology
Department of Laboratory Medicine
Lund Stem Cell Center
BMC B12, Lund University
221 84 Lund, Sweden
Phone: + 46 46 222 12 61
Mail:Goran [dot] Karlsson [at] med [dot] lu [dot] se