Associate Professor, UCSD Department of Medicine
M.D., Ph.D. University of Brisith Columbia, BC, Canada
Chronic myeloproliferative disorders and myelodysplastic syndromes have a propensity to evolve to acute myelogenous leukemia. This progression may be halted if the molecular events involved in disease progression and the stage of hematopoiesis at which they occur are elucidated and systematically blocked.
Since Dr. Jamieson's discovery of candidate cancer stem cells involved in progression of chronic myelogenous leukemia (CML) to acute leukemia, and the molecular events involved in enhancing CML cancer stem cell proliferation and self-renewal, she has devised robust methods to detect cancer stem cells in vivo, thereby permitting a comprehensive assessment of novel cancer stem cell diagnostics and therapeutics. She has applied molecular progenitor profiling, used for the discovery of cancer stem cells in advanced phase CML, to other myeloproliferative disorders and found that a specific mutation in the JAK2 signaling molecule occurs at the stem cell level in polycythemia vera and changes cell fate decisions in primitive hematopoietic cells.
Future studies will involve systematic molecular progenitor profiling combined with global gene expression profiling and a single cell FACS-based phosphoproteomics approach to identify the sequence of molecular events involved in progression of myeloproliferative disorders and myelodysplastic syndromes to acute leukemia with the ultimate aim of designing and testing novel cancer stem cell diagnostic and therapeutic strategies for use in MDS and MPD clinical trials at the Moores Cancer Center.
BMS Focus Areas:
1. Glycogen synthase kinase 3beta missplicing contributes to leukemia stem cell generation. Abrahamsson AE, Geron I, Gotlib J, Dao KH, Barroga CF, Newton IG, Giles FJ, Durocher J, Creusot RS, Karimi M, Jones C, Zehnder JL, Keating A, Negrin RS, Weissman IL, Jamieson CH. Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3925-9. Epub 2009 Feb 23. PMID: 19237556 [PubMed - indexed for MEDLINE]
2. Chronic myeloid leukemia stem cells. Jamieson CH. Hematology Am Soc Hematol Educ Program. 2008:436-42. Review. PMID: 19074122 [PubMed - indexed for MEDLINE]
3. Selective inhibition of JAK2-driven erythroid differentiation of polycythemia vera progenitors. Geron I, Abrahamsson AE, Barroga CF, Kavalerchik E, Gotlib J, Hood JD, Durocher J, Mak CC, Noronha G, Soll RM, Tefferi A, Kaushansky K, Jamieson CH. Cancer Cell. 2008 Apr;13(4):321-30. PMID: 18394555 [PubMed - indexed for MEDLINE]
4. The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation. Jamieson CH, Gotlib J, Durocher JA, Chao MP, Mariappan MR, Lay M, Jones C, Zehnder JL, Lilleberg SL, Weissman IL. Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6224-9. Epub 2006 Apr 7. PMID: 16603627 [PubMed - indexed for MEDLINE]
5. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. Jamieson CH, Ailles LE, Dylla SJ, Muijtjens M, Jones C, Zehnder JL, Gotlib J, Li K, Manz MG, Keating A, Sawyers CL, Weissman IL. N Engl J Med. 2004 Aug 12;351(7):657-67.