The overall objective of our project is to identify global genomic changes of clinical importance in leukemia, to increase our understanding of how genetic abnormalities in hematopoietic precursor cells result in leukemia, and to identify and characterize critical genes/proteins against which novel rational drugs ultimately can be designed.
Using genome-wide screening methods we have recently identified several candidate genes that are likely to be important in leukemogenesis. We are now applying multiple types of microarrays, next-generation sequencing techniques, and mathematical/statistical tools to characterize further various subtypes of leukemia and to correlate the findings with important clinical variables. Several already identified genetic changes are studied using various functional assays, including retroviral transduction of genetic changes into normal hematopoietic cells, followed by transplantation into NOD/SCID mice, and in shRNA-based silencing experiments in cell lines and primary cells.
Genome-wide studies of leukemia are likely to result in improved diagnostics, classification, and prognostication. Such studies, combined with functional studies in different experimental systems, should also provide important pathogenetic information and highlight alterations of critical genes/proteins towards which novel targeted therapies hopefully can be developed.
Thoas Fioretos, Professor, MD, PhD
Maria Askmyr, PhD, postdoc
Nina Larsson, MD, PhD
Henrik Lilljebjörn, Postdoc
Marianne Rissler, Research engineer
Anette Welin, Administrator
Helena Ågerstam, Postdoc
Selected recent publications:
Lilljebjörn H, Rissler M, Lassen C, Heldrup J, Behrendtz M, Mitelman F, Johansson B, Fioretos T. Whole-exome sequencing of pediatric acute lymphoblastic leukemia. Leukemia 2011 [Epub ahead of print]. Pubmed.
Järås M, Johnels P, Hansen N, Ågerstam H, Tsapogas P, Rissler M, Lassen C, Olofsson T, Weis Bjerrum O, Richter J, Fioretos T. Isolation and killing of candidate chronic myeloid leukemia stem cells by antibody targeting of IL-1 receptor accessory protein. Proc Natl Acad Sci USA 2010;107:16280- 5. Pubmed.
Ågerstam H, Järås M, Andersson A, Johnels P, Hansen N, Lassen C, Rissler M, Gisselsson D, Olofsson T, Richter J, Fan X, Ehinger M, Fioretos T. Modeling the human 8p11-myeloproliferative syndrome in immunodeficient mice. Blood 2010;116:2103-11. Pubmed.
Lilljebjörn H, Soneson C, Andersson A, Heldrup J, Behrendtz M, Kawamata N, Ogawa S, Koeffler HP, Mitelman F, Johansson B, Fontes M, Fioretos T. The correlation pattern of acquired copy number changes in 164 ETV6/RUNX1-positive childhood acute lymphoblastic leukemias. Hum Mol Genet. 2010;19:3150-8. Pubmed.
Järås M, Johnels P, Ågerstam H, Lassen C, Rissler M, Edén P, Cammenga J, Olofsson T, Bjerrum OW, Richter J, Fan X, Fioretos T. Expression of P190 and P210 BCR/ABL1 in normal human CD34(+) cells induces similar gene expression profiles in a STAT5-dependent expansion of the erythroid lineage. Exp Hematol 2009;27:367-375. Pubmed.
Andersson A, Olofsson T, Lindgren D, Nilsson B, Ritz C, Edén P, Lassen C, Råde J, Fontes M, Mörse H, Heldrup J, Behrendtz M, Mitelman F, Höglund M, Johansson B, Fioretos T. Molecular signatures in childhood acute leukemia and their correlations to expression pattern in normal hematopoietic subpopulations. Proc Natl Acad Sci USA 2005;102:19069-19074. Pubmed.
Networks in academia
Our research group is a part of the following strategic research programs:
- Hemato-Linne (Swedish Research Council Linneus Grant)
- BioCARE (Swedish Research Council Strategic Research Program)
Students and Positions
Highly motivated students interested in doing a project work (examensarbete) or a PhD are wellcome to contact professor Thoas Fioretos.
All postdoctoral and PhD positions are posted at the Lund University homepage.
Two spin-out companies have been established as a result of our research: