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December 2011 ISEH Newsletter
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Connections in Hematology & Stem Cells is supported by a grant from

In the December 2011 issue


Annual Scientific Meeting
An interview with the 2012 Scientific Program Committee chair.
Award winners announced.

Experimental Hematology
Explore key manuscripts in the November and December issues.

Society News
The value of belonging.

Member Profile
Meet Elaine Dzierzak, Ph.D., ISEH president-elect and 2012 Scientific Program Committee chair.



Annual Scientific Meeting

ISEH 41st Annual Scientific Meeting
23-26 August, 2012
Hotel Okura
Amsterdam, The Netherlands

 

Chair Elaine Dzierzak, Ph.D., Erasmus Medical Center Cell Biology Department, Rotterdam, Netherlands, and her committee members are in a strong position to attain their three overall goals for the 41st Annual Scientific Meeting:

  • To organize a program containing the best international researchers in the field of experimental hematology so as to inform members of the ISEH of their latest results.
  • To provide international visibility to young researchers by facilitating presentations and posters. In the future, these young investigators will lead the field of experimental hematology and the ISEH.
  • To promote interactions between researchers at all levels within our expanding global international community.

A robust slate of invited speakers has already been announced for the 2012 meeting including:

Donald Metcalf Lecture Award
Stuart Orkin, Dana-Farber Cancer Institute, Harvard Cancer Center, USA


McCulloch and Till Lecture Award
Timm Schroeder, Helmholtz Center Munich, Germany


Presidential Symposium

Alexander van Oudenaarden, Massachusetts Institute of Technology, USA
Ben Simons, University of Cambridge, UK


Developmental Biology (mammalian)

Nancy Speck, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, USA
Alexander Medvinsky, Institute for Stem Cell Research, University of Edinburgh, UK


Developmental Biology (other animal models)

Roger Patient, Weatherall Institute of Molecular Medicine, University of Oxford, UK
Thierry Jaffredo, Pierre and Marie Curie University, France


ES/iPS Cells

Gordon Keller, McEwen Centre for Regenerative Medicine, Canada
Hans Snoeck, Mount Sinai School of Medicine, USA
Luc Douay, Hôpitaux Universitaires Paris, Armand-Trousseau, France
Igor Slukvin, Hôpital Saint Antoine, USA


Epigenetics

Atsushi Iwama, Chiba University, Japan
Conny Bonifer, University of Birmingham, UK


Leukemia/Lymphoma

Mel Greaves, Institute of Cancer Research, UK
Tessa Holyoake, University of Glasgow, UK
Randy Gascoyne, BC Cancer Agency, Canada
Lou Staudt, National Institutes of Health, USA
Ari Melnick, Cornell University, USA


Microenvironment

Paul Frenette, Albert Einstein College of Medicine, USA
J.P. Levesque, Matter Medical Research Institute, Australia


Novel Tools/Approaches in Hematology

Peter Campbell, Wellcome Trust Sanger Institute, UK
Benjamin Ebert, Harvard University, USA
Frank Grosveld, Erasmus MC, Netherlands


Transcriptional/Translational Control of Hematopoiesis

Sjaak Philipsen, Erasmus MC, Netherlands
Marieke von Lindern, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands
Alan J. Warren, MRC Laboratory of Molecular Biology, UK


Transplantation/Gene Therapy/Regenerative Medicine

Marina Cavazzana-Calvo, Inserm, France
Stefan Karlsson, Lund University, Sweden

"All topics we chose for the meeting are emerging and exciting areas of study,” notes Dzierzak. "Scientifically, the Vancouver meeting was great! Our strategy is to continue to provide an excellent scientific program with a panel of speakers who are involved in the most recent and exciting findings in the field, such as the use of ES/iPS cells for blood cell production. The New Investigators Committee is active in choosing and inviting a speaker that will be involved in their career development activities. This year it is Derrick Rossi (Harvard). Also, improvements will be made in the poster organization and some of the social events so as to promote more interactions with young researchers.”

Dzierzak enjoys interacting and working with the knowledgeable committee members to make the Amsterdam ISEH meeting the best ever.

"I am excited about expanding the scope of scientific interest and expertise here in the Netherlands, particularly with the young researchers, by bringing the international experimental research community to Amsterdam,” she explains. "The Dutch hematologic research community has been active internationally for many years and I hope this legacy will continue, both scientifically and socially.”

She says that members of the Scientific Program Committee have broad interests in the field of experimental hematology and are involved in research at the fundamental, translational and clinical levels.

"A wide range of expertise (Ph.D., M.D., and M.D./Ph.D.) exists within the international committee, and encompasses molecular, developmental and cell biology, leukemia and lymphoma research as well as participation in clinical trials," Dzierzak offers.

The meeting location offers much to potential attendees.

"It is hard to compete with the natural, unspoiled beauty of Vancouver, but Amsterdam has a unique historical beauty built on the collaboration of man and the elements,” Dzierzak says. "The Netherlands is a formidable leader in hematologic research, both clinical and fundamental, and is an excellent site for the ISEH annual meeting. As an international hub city, Amsterdam is always a popular destination with its scenic canals, cafes and culture.”

Award Winners Announced

Congratulations to the 2012 award winners – watch for more information coming your way.

Donald Metcalf Lecture Award
Stuart Orkin - Dana Farber Cancer Institute and Harvard Stem Cell Institute, USA

McCulloch and Till Lecture Award
Timm Schroeder - Helmholtz Center Munich, Germany

They join a distinguished list of past recipients.


Coming Soon!

The ISEH 2012 Annual Scientific Meeting call for abstracts will open in February. Watch your e-mail for announcements.


2012 Scientific Program Committee

Elaine Dzierzak, chair (Netherlands)
Gerald de Haan (Netherlands)
Andrew Elefanty (Australia)
Tariq Enver (United Kingdom)
Peggy Goodell (USA)
Anthony Richard Green (United Kingdom)
Peter Lansdorp (Canada)
Kelly McNagny (Canada)
Toshio Suda (Japan)
Andreas Trumpp (Germany)


2012 Local Organizing Committee

Paul Coffer (Netherlands)
Jan Cornelissen (Netherlands)
Gerald de Haan (Netherlands)
Ruud Delwel (Netherlands)
Elaine Dzierzak (Netherlands)
Jurgen Kuball (Netherlands)
Jan Jacob Schuringa (Netherlands)
Ivo Touw (Netherlands)
Edo Vellenga (Netherlands)
Paula van Hennik (Netherlands)
Marieke von Lindern (Netherlands)


Experimental Hematology

Take a quick tour of the November and December issues and get a feel for the great scientific content. Read the full issues.

In this Issue – November 2011

A novel non-viral method of siRNA delivery into primary leukemia cells
Larsen et al
siRNA mediated knockdown of genes is a valuable tool to evaluate gene function in hematopoiesis and leukemogenesis, and therefore identification of highly effective non-viral method for siRNA delivery into such primary cells and cell lines is greatly desirable. In this study, Larsen et al compared a novel Accell methodology with Nucleofection, the current state of the art transfection method used for siRNA delivery into AML and CML primary cells and cells lines. They showed that the Accell method yielded superior transfection rates and cell viability. Surprisingly, however, improved transfection efficiencies did not translate to better gene knockdown for the two target genes they studied, hMICL and CD96. Additional studies targeting other genes and addressing the knockdown effect in functional assays are needed to determine whether such a promising methodology of non-viral siRNA delivery could be widely used for primary hematopoietic and leukemic cells.

Can the number of PSGL-1 positive microparticles in the blood be a useful prognostic marker?
Trummer et al
The interaction of P-selectin with its receptor P-selectin glycoprotein Ligand 1 (PSGL-1) plays an important role in hematopoiesis, as a negative regulator, and in cancer growth and metastasis. P-selectin also plays a role in graft versus host disease (GvHD) by promoting T cell activation, and P-selectin negative mice have a decreased incidence of mortality due to GvHD. Microparticles (MPs) are submicron-size vesicles released from cell membranes in response to activation or apoptosis. In this study, Trummer et al measured, by flow cytometry, the number of PSGL-1 positive MPs in the blood of patients undergoing allogeneic stem cell transplantation (alloSCT). They showed that patients with higher PSGL-1 MPs at two of the time points measured, at graft infusion and engraftment had a shorter time to engraftment, whereas those with lower PSGL-1 MPs may have a higher risk of relapse following alloSCT. The test described here, simple and noninvasive, with prognostic value is highly anticipated in the field, and needs to be prospectively validated in a larger cohort.

The transcription factor Mxd4: an important player during embryonic hematopoietic differentiation
Boros et al
The essential role of c-Myc within Myc-Max-Mad interaction in embryonic hematopoiesis is well documented. c-Myc knockout mouse embryos do not generate definitive hematopoiesis, and die at E9.5. However, not much is known about the role that Mad proteins (Mxd1, Mxi1, Mxd3, and Mxd4), functional antagonists of Myc function, play in hematopoietic differentiation. In this study, Boros et al, first documented a tightly regulated pattern of Mxd4 expression during embryonic development, and consequently showed that forced expression of Mxd4 at this stage resulted in impaired development of both primitive and definitive blood lineages, due to a significantly decreased in cell proliferation. This provides indirect evidence that indeed, downregulation of Mxd4 expression might be required at an early stage of commitment to the hematopoietic lineage, so that a proliferative burst can occur prior to lineage specification. Such studies provide a valuable resource that will enhance our understanding of embryonic hematopoiesis.

CCL8: a potential prognostic marker for acute graft-vs.-host disease (GVHD)
Yamamoto et al
The current diagnosis of GvHD rely on clinical and histopathological findings. A biomarker that will facilitate early and accurate diagnosis and the initiation of appropriate therapy in a timely manner will be very useful for clinicians. CC-chemokine ligand motif 8 (CCL8), a member of a large chemokine family, was recently identified as a potential biomarker for the diagnosis of GvHD in mice and humans. Upon treatment with cyclosporin A, CCL8 protein levels decreased and the clinical findings of GvHD improved. In this study, Yamamoto et al showed that the plasma CCL8 levels in mice early after transplantation (on day 5 post transplant) in the absence of any signs of GvHD, closely correlated with survival rate and clinical and pathological scores on day 14. Measuring plasma CCL8 at an early time point after transplantation as a potential prognostic marker for GvHD can become a useful tool for the clinicians, once the promising preclinical findings are confirmed prospectively in a large cohort of patients undergoing allogeneic stem cell transplantation.


In this Issue – December 2011

A novel cellular therapy to treat Hemophilia A
Porada et al
Hemophilia A (HA) is an ideal candidate for treatment with gene therapy because it is a monogenic disorder and a small increase of 2-3% in the endogenous FVIII level can result in therapeutic benefit. The safety and efficacy of gene therapy have been demonstrated in murine and large animals models of HA using various gene transfer strategies, but the results of several phase I clinical trials have been disappointing, in part due to the development of inhibitors to vector derived FVIII in treated patients. In this study, Porada et al showed phenotypic conversion of severe HA to a moderate phenotype in 2 non-ablated post-natal sheeps and complete reversal of crippling hemarthroses present at the time of treatment following intraperitoneal transplantation of mesenchymal stem cells (MSC) engineered to produce FVIII. Despite the favorable outcome, surprisingly, however; both sheeps developed high-titer inhibitors to the vector-encoded FVIII and never had any detectable FVIII in the circulation. Mechanistic studies that could help to understand and overcome the formation of inhibitors are urgently needed, so that such a promising, safe and effective therapeutic modality can be offered as a treatment option to patients with hemophilia.

Regulatory T cells; which ones are the best?
Ukena et al
Regulatory T cells (Tregs) prevent autoimmunity and limit aggressive immune responses directed against foreign antigen that might damage host tissue. The immunoregulatory function of these cells makes them ideal therapeutic candidates for: the treatment of autoimmune diseases; prevention and treatment of GvHD, and prevention of organ transplant rejection. There are several ongoing phase I/II clinical trials addressing their efficacy in the prevention of GvHD, prevention of kidney transplant rejection and treatment of type 1 diabetes. In those trials, Tregs are isolated based on their CD4 and CD25 expression (CD4+CD25+), but the isolation of highly effective Tregs can further be improved. In this study, Ukena et al wanted to define the most promising Treg target cell population for cellular therapies with respect to their phenotype, suppressive function, stability and expansion capacity. They demonstrated that the freshly isolated Tregs that show the highest suppressive capacity and best phenotypic stability of Foxp3 expression do not express CD127 (CD4+CD25+CD127-) and express ICOS (CD4+CD25+ICOS+). Their findings suggest that future clinical trials should favor CD4+CD25hiCD127- and CD4+CD25hiICOS+ Tregs for direct Treg cell transfer, whereas CD4+CD25hi Tregs should be preferred for in vitro expansion, as they readily expand to desirable numbers while maintaining their phenotype and strong suppressive potential. Identifying the right target Tregs for clinical trials in GvHD, transplant rejection prophylaxis and therapy, as well as for the treatment of autoimmune disorders, is crucial to improve their efficacy and outcome.

hTERT in childhood acute lymphoblastic leukemia
Borssén et al
Telomeres are DNA structures, which serve to stabilize chromosomes. The human telomerase reverse transcriptase ( hTERT ) is the catalytic component of telomerase, the enzyme required for the maintenance of telomeres. Human cells express low levels of telomerase, and abnormal activation of telomerase can lead to immortalization and uncontrolled proliferation, a process that has been associated with the development of many leukemias and lymphomas. In this study, Borssén et al investigated the biological and clinical significance of telomere length and promoter methylation status of the hTERT gene in pediatric acute lymphoblastic leukemia. They showed that telomeres were shorter at diagnosis than at the end of therapy (blast cells had shorter telomeres than normal hematopoietic cells) and only in the low-risk B-cell precursor (BCP) ALL group, telomere length had a prognostic implication, which indicated that patients with long telomeres had a worse prognosis. The hTERT promoter was methylated in 24 % of samples, both T- cell ALL and [ETV6/RUNX1] positive BCP ALL cases showed a significantly higher frequency of hTERT methylation. However, due to the small number of patients analyzed, a relationship between survival and hTERT methylation status could not be established. Further studies deciphering the biological and clinical significance of hTERT methylation in ETV6/RUNX subgroup of B-ALL and T-ALL cases may lead to the discovery of therapies targeting the telomere/telomerase complex.

Submit a Manuscript

When is the last time you submitted a manuscript to Experimental Hematology? It is likely time to spread the wealth of your knowledge once again.


The publishing team seeks manuscripts describing research involving in vivo and ex vivo studies in the following areas: cell cycle regulation, cytokines, erythropoiesis, gene therapy, general hematopoiesis, granulopoiesis, hematological malignancies, immunobiology, immunotherapy, lymphopoiesis, megakaryocytopoiesis, microenvironment, monocyte development, molecular genetics, signal transduction, stem cell biology, and experimental as well as clinical stem cell transplantation.

Visit the Experimental Hematology website for more information.

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Society News

Rich History Provides Membership Incentive!

How important is it to belong to ISEH? Think about this line from the ISEH history posted on the website:

"ISEH members were first to describe every known in vitro and in vivo assay for hematopoietic stem cells and progenitor cells (in vitro CFU-S, CFU-C, LTC-IC, CAFC assays and innovative in vivo transplantation assays).”
Be there when it happens. Renew for 2012 and also obtain these benefits:

• Easy access to more than 800 members, your colleague researchers in the field
• A personal subscription and exclusive full-text online access to the journal, Experimental Hematology, including supplements and abstracts for ISEH-supported meetings.
• No manuscript submission fee for Experimental Hematology. This offer is valid for corresponding authors of submitted manuscripts.
• ISEH Connections in Hematology & Stem Cells, your ISEH electronic newsletter, the exclusive source for Society, member and industry news.
• Reduced registration fees at the ISEH Annual Scientific Meeting and other selected educational events organized or supported by ISEH.
• Eligibility for ISEH awards and travel grants.
• Full access to enhanced website. You are now connected through instant messaging to members who are online, posting to colleagues’ walls, reading articles on featured membership profiles and responding to discussion forums.
• An opportunity to serve on ISEH Committees and the Board of Directors.

When you renew on the ISEH website , be sure to also update your member profile, so that members and staff know how to reach you. 

 

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Member Profile

ISEH, comprised of industry leaders in hematology, immunology, stem cell research, and cell and gene therapy, connects members worldwide for the opportunity to advance scientific knowledge. Each issue of Connections in Hematology & Stem Cells will introduce you to those members. This issue, meet Elaine Dzierzak, Ph.D., Erasmus Medical Center, Erasmus Stem Cell Institute, Rotterdam, Netherlands.

ISEH President-Elect Values Society Collaboration

Elaine Dzierzak, Ph.D.
Erasmus Medical Center
Erasmus Stem Cell Institute
Rotterdam, Netherlands


ISEH President-Elect Elaine Dzierzak, Ph.D., is professor of developmental biology in the department of Cell Biology at Erasmus University  and director of the Erasmus Medical Center Stem Cell Institute. As noted in the Annual Scientific Meeting article above, she is also chair of the 2012 Scientific Program Committee tasked with delivering this important meeting.

Not a problem for a woman whose career track has taken her to several countries and numerous prestigious institutions working within various disciplines.

"I initially started my research career as an immunologist,” Dzierzak explains. "My Ph.D. work at Yale University (New Haven, CT, USA) was on immunoglobulin specificity and idiotypes. These studies introduced me to mouse genetics. From there, I went on to do research on retroviral mediated gene delivery at the Whitehead Institute (Cambridge, MA, USA). By using in vivo mouse models of hematopoiesis, I found that the difficulty in most therapeutic approaches to hematopoietic disease is in the manipulation and expansion of hematopoietic stem cells. This gave me the idea of looking towards developmental processes to establish how hematopoietic stem cells are made in the embryo.”

Dzierzak was the first to demonstrate the expression of a retrovially transduced therapeutic gene in hematopoietic stem cells (HSC) after bone marrow stem cell transplantation. After moving to the National Institute for Medical Research (London), she changed the long-held textbook dogma of the yolk sac origins of the adult hematopoietic system, showing that adult-type HSCs are generated from the embryonic aorta.

"Since we have demonstrated that hematopoietic stem cells are generated from hemogenic endothelium, our current studies focus on identifying the sequential expression of a number of pivotal transcription factors in the hemogenic endothelium and the downstream targets that are involved in the endothelial to hematopoietic transition,” she continues. "We will do this through our advanced embryo imaging methods and new mouse marker/mutant models.”

The ISEH Annual Scientific Meeting is among the important stimuli to her scientific work. It is also the place where she gets some ideas on meeting the challenges of her professional life – how to balance one’s personal and professional life and how to address the funding challenges due to the global economic crisis.

"For me the annual ISEH meeting is an extremely important conference,” she says. "I see many of my closest collaborators and colleagues, and I meet many young researchers. It is an energizing meeting that stimulates new ideas and an urgency to get back to the lab to start new experiments. I particularly enjoy the poster sessions, scientific and social interactions and the banquet, where I can dance with the students, postdocs and former ISEH presidents, especially dancing with whoever comes out on the dance floor like Thalia (Papayannopoulou) and Toshio (Suda).”

Music is important to Dzierzak.

"When not involved in science, I enjoy listening to music and going to concerts with my family and friends; we are big Bob Dylan fans,” she offers. "I also love to cook, especially with fresh seasonal vegetables and fruits when we are in the South of France for our holidays.”

Look for Elaine Dzierzak on the dance floor in Amsterdam. Or, connect with her now through the ISEH member database. Click here to learn more about her or to build your personal profile. You can also learn more about the Erasmus Medical Center Stem Cell Institute.

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