Molecular signatures of quiescent, mobilized and leukemia-initiating hematopoietic SC

Molecular Signatures of Quiescent, Mobilized and Leukemia-Initiating Hematopoietic Stem Cells by E Camilla Forsberg and 6 co-authors, including Irving L Weissman, PLoS One 2010(Jan 20);5(1):e8785. [Connotea bookmark][FriendFeed entry][Full text is publicly accessible (via Libre OA)]. PubMed Abstract:

Hematopoietic stem cells (HSC) are rare, multipotent cells capable of generating all specialized cells of the blood system. Appropriate regulation of HSC quiescence is thought to be crucial to maintain their lifelong function; however, the molecular pathways controlling stem cell quiescence remain poorly characterized. Likewise, the molecular events driving leukemogenesis remain elusive. In this study, we compare the gene expression profiles of steady-state bone marrow HSC to non-self-renewing multipotent progenitors; to HSC treated with mobilizing drugs that expand the HSC pool and induce egress from the marrow; and to leukemic HSC in a mouse model of chronic myelogenous leukemia. By intersecting the resulting lists of differentially regulated genes we identify a subset of molecules that are downregulated in all three circumstances, and thus may be particularly important for the maintenance and function of normal, quiescent HSC. These results identify potential key regulators of HSC and give insights into the clinically important processes of HSC mobilization for transplantation and leukemic development from cancer stem cells.

SC-derived gene expression profiles predict poor outcome for AML patients

Leukemic and Normal Stem Cell Transcriptional Signatures Determined by Functional Assays Are Predictive of the Overall Survival of AML Patients by Kolja Eppert and 11 co-authors, including John E Dick, Abstract #389, 51st ASH Annual Meeting, December 7, 2009. Final sentence:

Together these data support the hypothesis that the biological determinants that underlie stemness in both normal and leukemic cells are predictors of poor outcome, and are potential targets for novel therapy.

Gene signatures in residual breast cancers after conventional therapy

Gene Signature of Breast Cancer Stem Cells Revealed, Genetic Engineering & Biotechnology News, August 4, 2009. First paragraph:

A consortium of researchers have identified the gene expression patterns of breast cancer stem cells that remain post treatment with either chemotherapy or antihormone treatments. They report that this gene signature differs from those linked to the bulk of epithelial cells in the tumor.

Based on: Gene signature for cancer stem cells may provide drug targets, Glenna Picton, News Release, Baylor College of Medicine, August 4, 2009.

See also: Gene signature for cancer stem cells may provide drug targets, Science Centric, August 4, 2009. First paragraph:

A subset of tumour cells that remain after a woman with breast cancer undergoes treatment with either anti-cancer or anti-hormone therapy shows a 'gene signature' that could be used to define targets for developing new drugs against the disease, said a consortium of researchers led by Baylor College of Medicine. The report appears in the current issue of the Proceedings of the National Academy of Sciences.

The report referred to in the above excerpt is an Open Access publication: Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features by Chad J Creighton and 22 co-authors, including Michael T Lewis, Jeffrey M Rosen and Jenny C Chang, Proc Natl Acad Sci USA 2009(Aug 3). [Epub ahead of print].[Abstract][Early version of OA full text].

Differentially expressed genes in cell lines of differing lymphatic metastatic ability

Lymphatic metastasis of breast cancer cells is associated with differential gene expression profiles that predict cancer stem cell-like properties and the ability to survive, establish and grow in a foreign environment by Terlika S Pandit and 11 co-authors, including Ann F Chambers and Alan B Tuck, Int J Oncol 2009(Aug); 35(2): 297-308. [FriendFeed entry]. PubMed Abstract:

Although lymphatic dissemination is a major route for breast cancer metastasis, there has been little work to determine what factors control the ability of tumor cells to survive, establish and show progressive growth in a lymph node environment. This information is of particular relevance now, in the era of sentinel lymph node biopsy, where smaller intranodal tumor deposits are being detected earlier in the course of disease, the clinical relevance of which is uncertain. In this study, we compared differentially expressed genes in cell lines of high (468LN) vs. low (468GFP) lymphatic metastatic ability, and related these to clinical literature on genes associated with lymphatic metastatic ability and prognosis, to identify genes of potential clinical relevance. This approach revealed differential expression of a set of genes associated with 'cancer stem cell-like' properties, as well as networks of genes potentially associated with survival and autonomous growth. We explored these differences functionally and found that 468LN cells have a higher proportion of cells with a cancer stem cell-like (CD44+/CD24-) phenotype, have a higher clonogenic potential and a greater ability to survive, establish and grow in a foreign (lymph node and 3D Matrigel) microenvironment, relative to 468GFP cells. Differentially expressed genes which reflect these functions provide candidates for investigation as potential targets for therapy directed against early lymphatic metastasis.