About AML and CML

1) First Genome-Wide Expression Analysis Yields Better Understanding of Leukemia, News Release, University of Rochester Medical Center, February 10, 2009.

Genome-wide leukemia analysis completed, UPI Science News, February 11, 2009.

These news items are about the article: Dysregulated gene expression networks in human acute myelogenous leukemia stem cells by Ravindra Majeti and 9 co-authors, including Michael W Becker, Leroy Hood, Michael F Clarke and Irving L Weissman, Proc Natl Acad Sci USA 2009(Feb 13) [Epub ahead of print][PubMed Citation][Version in PMC].

2) Scientists Uncover indicator that Warns leukemia is Progressing to more dangerous form by Steve Benowitz, News Release, UC San Diego News Center, February 17, 2009.

This news release is about the article: Glycogen synthase kinase 3{beta} missplicing contributes to leukemia stem cell generation by Annelie E Abrahamsson and 15 co-authors, including Armand Keating, Robert S Negrin, Irving L Weissman and Catriona H M Jamieson, Proc Natl Acad Sci USA 2009(Feb 23) [Epub ahead of print][PubMed Citation][Full text PDF].

More on financial outlook for CIRM

CIRM Touts Its Financial Outlook by David Jensen, California Stem Cell Report, February 17, 2009. Excerpts:

CIRM has officially but quietly announced that it hopes to raise $400 million through 2010 by selling California state bonds privately, a task never before achieved in state history.

The information on the private placement goal was posted Friday on the CIRM web site with virtually no notice or fanfare. ...

.....

While the agency is now about seven months away from running out of cash, the Friday item has a positive headline, "CIRM's Financial Commitments Are Secure." The language is tailored to reassure grant applicants, especially those applying for the $210 million disease team RFA that was also posted on Friday.

[For information about the Disease Team RFA, see this previous post: CSCC and CIRM announce a Collaborative Funding Partner Program, February 15, 2009].

Elimination of CSC in a mouse model of CML

Targeting a chronic problem: elimination of cancer stem cells in CML by Claus Nerlov, EMBO J 2009(Feb 4); 28(3): 167-8 [PubMed Citation][Openly accessible full text][Version in PMC]. First paragraph:

The eradication of tumours by targeting malignant stem cell populations, or cancer stem cells (CSCs), is a promising new strategy for cancer treatment. In a paper published in a recent issue of The EMBO Journal, pharmacogenetic evidence has been obtained that this is indeed feasible in a mouse model of human chronic myeloid leukaemia. These and further similar experiments will be essential to determine the validity and practical usefulness of the CSC hypothesis.

This article is a commentary about: Cancer induction by restriction of oncogene expression to the stem cell compartment by María Pérez-Caro and 12 co-authors, including Isidro Sánchez-García, EMBO J 2009(Jan 7); 28(1): 8-20 [Epub 2008(Nov 27)][PubMed Citation][Openly accessible full text][Version in PMC]. Excerpt from the last paragraph of the Discussion section of the full text:

The data presented here further show for the first time the in vivo physiological relevance of the CSC suppression using a model system representing in vivo biology of the human CML disease. .....

CSCC and CIRM announce a Collaborative Funding Partner Program

Collaborative Funding Partner Program announced by The California Institute for Regenerative Medicine and the Cancer Stem Cell Consortium, CSCC News & Media, February 13, 2009. (Archived by WebCite® at http://www.webcitation.org/5ebckolB9). Excerpt:

The California Institute for Regenerative Medicine (CIRM) is pleased to announce a Collaborative Funding Partner Program with Cancer Stem Cell Consortium (CSCC) through CIRM's RFA 09-01 Disease Team Research Award. The purpose of this initiative is to support the research of multi-disciplinary teams of scientists, co-led by Canadian and Californian Principal Investigators that will result in a cancer stem cell based therapy or a therapy derived from cancer stem cell assays with the specific aim of improving cancer treatment.

For details of the CIRM Disease Team Research Award RFA 09-01 please go to (http://www.cirm.ca.gov/RFA/rfa_09-01/default.asp).

French version available in PDF format.

Under this RFA 09-01, the CSCC intends to commit up to CDN$40 million to support the Canadian component of up to two (2) projects funded through the Collaborative Funding Partner Program. Projects will be funded for up to four (4) years, with justifiable total Canadian project costs of up to CDN$20 million per project, conditional upon CIRM funding up to US$20 million per project to support the Californian component.

Teams of Canadian and Californian scientists submitting applications to CIRM's Disease Team Research Award RFA through the Collaborative Funding Partner Program must complete both the CIRM requirements and any additional requirements put forth by the CSCC.

This collaborative initiative with CIRM is the first opportunity for funding available to Canadian scientists through the CSCC. As the CSCC develops its research program it is guided by the CSCC Scientific Strategic Plan. The Canadian scientific community will be kept informed of additional opportunities for funding as they are developed.

For details of the CIRM Disease Team Research Award RFA 09-01 please go to (http://www.cirm.ca.gov/RFA/rfa_09-01/default.asp).

NOTE: Participation in this RFA is NOT limited to scientists who registered with the CSCC their intent to submit an application to the Disease Team Research Awards Competition.

For information about the CSCC-CIRM Collaborative Funding Partner Program contact:

Cindy L. Bell, Ph.D.
Interim Executive Director, CSCC
Email: cscc@genomecanada.ca
Phone: (613) 751-4460 ext 118

(RFA 09-01: CIRM Disease Team Research Awards archived in PDF format by WebCite® at http://www.webcitation.org/5ebdf0wi0).

(French version of news release archived in PDF format by WebCite® at http://www.webcitation.org/5ebeFwit5).

Connotea: CSC-related tags

A few different keywords have been used to tag articles about cancer stem cells on the Nature Publishing Group's Connotea free online reference management site. The keywords include:

"Cancer SC": A total of 222 references were tagged with these keywords on February 14, 2009.
"Leukemic SC": 78 references.
"cancer stem cells": 32 references.
"cancer stem cell": 31 references.
"CSC": 28 references.
"cancer-stem-cells": 3 references.

All of these tags combined: A total of 388 references were tagged with one or more of these keywords on February 14, 2009. (The sum of the totals for all of these tags is 394, so there was an overlap of tags for 6 of the references).

These references to articles related to cancer stem cells have been posted by a total of 41 Connotea users.

On recent articles from Stanford about CSC

1) Leukemia Stem Cells Have More In Common With Embryonic Stem Cells Than Adult Stem Cells, ScienceDaily, February 5, 2009. First sentence:

Research using a mouse model of human leukemia has provided critical insight into the genetic factors related to the generation and maintenance of myeloid leukemia stem cells.

Cell find 'lifts leukaemia fight', BBC News, February 6, 2009. Leading sentence:

Research which sheds light on how blood cancer cells work may improve the power of leukaemia treatments.

Research which sheds light on how blood cancer cells work may improve the power of leukaemia treatments, Euro News 24, February 6, 2009.

These news items are about this article: Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells by Tim C P Somervaille and 9 co-authors, including Michael L Cleary, Cell Stem Cell 2009(Feb 6); 4(2): 129-40 [PubMed Citation][Full text].

Preview: The MLLgnant Consequences of Reverting to an Embryonic Transcriptional Program by Catriona Jamieson, Cell Stem Cell 2009(Feb 6); 4(2): 97-8 [Full text]. Leading sentence:

In this issue of Cell Stem Cell, Somervaille etal., 2009 have demonstrated convincingly that reversion to an embryonic transcriptional program through defective MLL gene expression contributes to the generation of myeloid leukemia stem cells.

2) Source of cancer stem cells' resistance to radiation discovered at Stanford by Krista Conger, News Release, Stanford School of Medicine, February 4, 2009. [Includes a 4-minute video]. First paragraph:

Much to the dismay of patients and physicians, cancer stem cells — tiny powerhouses that generate and maintain tumor growth in many types of cancers — are relatively resistant to the ionizing radiation often used as therapy for these conditions. Part of the reason, say researchers at Stanford University School of Medicine, is the presence of a protective pathway meant to shield normal stem cells from DNA damage. When the researchers blocked this pathway, the cells became more susceptible to radiation.

Breakthrough Made On Cancer Stem Cell Source, CBS Broadcasting, February 5, 2009. (Also includes a video).

How breast cancer resists treatment, Monya Baker, Nature Reports Stem Cells, 5 February 2009.

These news items are are about this article: Association of reactive oxygen species levels and radioresistance in cancer stem cells by Maximilian Diehn, Robert W Cho and 21 co-authors, including J Martin Brown, Irving L Weissman and Michael F Clarke, Nature 2009(Feb 4) [Epub ahead of print][PubMed Citation].

Added February 24, 2009: Cancer stem cells: Survival skills by Sarah Seton-Rogers, Nature Reviews Cancer 2009(Mar); 9: 147.

Added May 19, 2009: See also: Source of cancer stem cells’ resistance to radiation discovered at Stanford, posted by Stem Man to "Latest Stem Cell News" on 19 May 2009. The post also provides access to another video that was posted to YouTube on February 12, 2009.

3) Cancer stem cell-directed therapies: recent data from the laboratory and clinic by Christopher Y Park, Diane Tseng, Irving L Weissman, Mol Ther 2009(Feb); 17(2): 219-30 [Epub 2008(Dec 9)][PubMed Citation][Full text]. First paragraph from the Final Words section of the full text:

Although CSCs have been identified in numerous human cancers, whether or not CSC-directed therapies will ultimately lead to cures remains an open question. Although this issue will, no doubt, be the focus of investigations for years to come, the studies described herein indicate that CSCs are likely to fulfill several of the predictions of the CSC hypothesis: (i) that CSCs are relative resistant to conventional therapies and (ii) that clinical outcomes will correlate with measurable CSC parameters including frequency, localization, and gene signatures. Based on these observations, we think CSC-directed therapies show great promise for improving clinical outcomes, but it will be important for researchers to verify these properties for CSCs in each tumor type since they likely will not be uniform with respect to their biologic properties, consistent with their heterogeneous molecular origins.

Scientific Strategic Plan for the CSCC

The Scientific Strategic Plan 2009-2014 for the Cancer Stem Cell Consortium (CSCC) is available, via the Strategic Plan section of CSCC website. The 26-page plan is dated October 9, 2008 [PDF].

Executive Summary

The discovery of a rare subpopulation of tumor cells, termed cancer stem cells (CSCs), in many common malignancies has profound implications for treating cancer patients. Most current anticancer therapies were developed to kill the major tumor cell population that makes up the bulk tumor mass; however, these cells are not responsible for the growth and dissemination of tumors. CSCs are at the root of cancer and account for tumor growth and metastases. CSCs are resistant to the toxic effects of radiation therapy and current chemotherapies. Hence, it is not surprising that tumors often recur, leading to relapse of cancer patients treated with these agents. By developing new therapies that target CSC for eradication, long-lasting cures should be achieved.

According to a recent economic report, a 1% reduction in mortality from cancer would save nearly $500 billion to current and future Canadians and Americans. A “war on cancer,” which would cost an additional $500 million for CSC research and treatment over the next 5 years, would clearly yield an excellent return on investment.

Both Canadian and Californian researchers pioneered the discovery of CSCs giving them a powerful historical lead in this rapidly expanding field. Moreover, a significant percentage of the world’s CSC researchers are located in Canada and California. Thus, there is a natural alignment of research prowess and critical mass of researchers in both jurisdictions with which to surmount the challenges posed by CSCs.

The CSC Consortium’s research programs will focus on identifying CSC biomarkers and anti-CSC therapeutic agents. State-of-the-art infrastructure will provide live CSCs from various malignancies for study. This plan also envisions developing a number of novel high-throughput technologies. The scientific community believes that progress will occur more rapidly by supporting several large-scale efforts involving multiple Research Teams (see Figure 3), that will share cutting-edge core Technology Platforms and Facilities and common research goals to generate new knowledge. The CSC Consortium, a not-for-profit corporation with a strong governance and management structure, will provide funding and oversight of the research programs and supporting infrastructure.

This strategic plan recommends that the CSC Consortium invest significantly in translational activities that will accelerate the evaluation of CSC-specific biomarkers and the discovery of anti-CSC therapies. Both Canada and California host Comprehensive Cancer Centres that will provide the infrastructure necessary to validate CSC biomarkers and to clinically evaluate new anticancer therapies targeting CSCs including “First-in-Man” studies.

This plan describes strategically important CSC research and technology programs, and proposes CSC Consortium activities and an organizational structure to manage a budget of sustained and stable funding of $500 million (CDN) for an initial five-year period, which will be provided by a variety of agencies in Canada and California. Sustained funding is the key to the success of the CSC Consortium because of the unique nature of the expertise and technologies required for this research, and the imperative for rapidly moving discoveries to the clinic. CSC Consortium funding will be bolstered by world-leading business expertise and will lead an exciting wave of new biotechnology companies based on CSC discoveries.

Pointers for future research on CSC

Looking ahead in cancer stem cell research by John E Dick, Nat Biotechnol 2009(Jan); 27(1): 44-6 [PubMed Citation]. Leading sentence:

The history of the stem cell field offers pointers for future research on cancer stem cells.

The full text is publicly accessible. Excerpts:

Since the beginning of the era inaugurated by the great experimental pathologists, microscopic examination has revealed that many tumors, be they liquid or solid, exhibit morphologic heterogeneity. Tumors are also heterogeneous functionally, as demonstrated most dramatically by studies in which murine or human tumors were re-transplanted into syngeneic or xenogeneic immune-compromised recipients. Remarkably, such experiments have also included human autotransplants. The collective conclusion from these studies was that tumor re-initiation is variable and often rare, requiring 10³ to 10⁷ cells.

.....

Ultimately, the relevance of the CSC model will be determined by clinical data.

See also:

The CSC hypothesis: recalling some history (December 30, 2008).

Tumorigenic cells not rare in human melanoma (December 3, 2008).

Two recent articles about cancer stem cells

1) Cancer stem cells: A guide for skeptics by Michael H Tomasson, J Cell Biochem 2009(Jan 30) [Epub ahead of print][PubMed Citation]. The full text of this article isn't publicly accessible.

2) Stemness, cancer and cancer stem cells by David J Wong, Eran Segal, Howard Y Chang, Cell Cycle 2008(Dec); 7(23): 3622-4 [Epub 2008(Dec 2)][PubMed Citation]. The full text of this article is publicly accessible [PDF].