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

In the April 2011 issue

Annual Scientific Meeting 
Make plans for Vancouver, 25-28 August! Important dates and passport/visa information provided.

Experimental Hematology 
Explore key manuscripts in the April issue.

Young Investigators
Committee slates activities at 40th Annual Scientific Meeting.

Society News
ISEH opens call for nominations 3 May.

Applications due 10 May for $50,000 fellowship.

News from the Field 
What do you want to see in Connections?

Member Profile
Learn about Grover Bagby, former ISEH president and current Publications Committee chair.

 

 

 

Annual Scientific Meeting

Make Plans for Vancouver!

 

40th Annual Scientific Meeting

25-28 August, Westin Bayshore Hotel, Vancouver, Canada

The vibrant local hematology and stem cell community in Vancouver makes this thriving international city a great spot for the ISEH Annual Scientific Meeting. It is convenient for our members traveling from Asia Pacific and North America, and the August timeframe allows our European members to attend at the end of holiday season.

This is, of course, only a complement to the outstanding science one expects from the ISEH Annual Scientific Meeting.

"As an experimental hematologist, I expect to attend a meeting where I will hear and discuss many interesting topics and where I will be able to present and discuss topics in my primary point of interest – pharmacological modulation of hematopoietic cell proliferation,” states Michal Hofer, MD, PhD, an early registrant and assistant professor, Laboratory of Experimental Hematology, Institute of Biophysics, Academy of Science, Czech Republic.

"I have attended several ISEH meetings in the past and wanted to attend once again this year. This is a hematopoietic focused meeting of good scientific quality with good basic research and some insight in new development in clinics,” says Veronique Maguer-Satta, PhD, Cancer Research Center of Lyon (CRCL), Lyon, France. "Also as an old Connie Eaves post-doc, it will be nice to come back 15 years later to that wonderful place!”

The Annual Scientific Meeting schedule is jam-packed with short talks, invited speakers, poster presentations and networking time. View the current speaker lineup.

One key networking event is the Saturday night Harbour Princess cruise, supported by STEMCELL Technologies Inc. Eat, drink, dance and visit with your colleagues as you see the beautiful sights of Vancouver. Space is limited, so be sure to register promptly to ensure your spot.

Passports/Visas

Now would be a great time to be sure you have the documentation required to travel to Canada. More information, including how to apply for a visa, is available on the ISEH website, but a few reminders:

Countries requiring visas are listed on the Citizenship and Immigration Canada website.

While not a difficult process, applying for a visa takes time. Learn how to apply.

Travelers from the United States are now required to have a passport to enter Canada. Learn how to obtain a passport.

ISEH has applied to the Canadian Border Services Agency for recognition, which would exempt non-Canadian ISEH attendees from needing a work permit. Watch for more information on the letter of recognition you should print to present to the Border Services officer.

Important Dates

29 April - Abstract Submission Deadline
This is a firm deadline! Submit your abstract today.

24 June – Early Bird Registration Deadline
Save up to $175 – register today.

Be sure to also make your hotel reservations at the Westin Bayshore Vancouver at the ISEH rate of CAD $199.

10 June-8 July – Late Breaking Abstract Submission
Watch for information on this opportunity to submit works not yet complete.

25-28 August – Annual Scientific Meeting
Full details on the ISEH website.


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Experimental Hematology

Your society journal continues to offer the latest on research in the fields of hematopoietic stem cells, hematologic malignancies and the exciting emerging areas of model organisms and genomics as applied to normal and malignant hematopoiesis. Take a quick tour of the April issue.

In this Issue – April 2011

The Flt3 internal tandem duplication (Flt3-ITD) alters chemotherapy response
Pardee et al

Mutations of the FLT3 receptor gene are among the most common molecular abnormalities in AML and the presence of Flt3-ITD has been associated with worse prognosis by many groups. Previous in vitro studies have associated the Flt3-ITD with resistance to anthracyclines. This observation has been supported by a recent clinical trial in which only patients with the Flt3-ITD failed to benefit from intensified anthracycline dosing regimen. Moreover in a murine model of leukemia expressing PML-RARa and Flt3-ITD, inhibition of the Flt3-ITD resulted in increased sensitivity to anthracyclines providing further evidence for this relationship. In their study, Pardee et al provide further evidence that the Flt3-ITD confers sensitivity to cytarabine and resistance to doxorubicin in a MLL-ENL driven mouse leukemia suggesting that patients with Flt3-ITD positive AML may not benefit from anthracyclines in the absence of a Flt3 inhibitor. It remains to be shown that this is true for all patients with Flt3-ITD. In that case treatment regimens for these patients need to be reevaluated and Flt3 inhibitors should be incorporated urgently in their treatment regimens.

A new target in human immune thrombocytopenia (ITP): The CD47 pathway
Catani et al

Understanding the mechanism involved in the antibody mediated platelet destruction in ITP will be valuable in finding cure for patients with refractory disease. It has been shown that the interaction between CD47 antigen on platelets and its ligand SIRPa on macrophages play an important role in platelet hemostasis by inhibiting phagocytosis as well as in a mouse model of ITP. Mice with CD47 and SIRPa deficiency are thrombocytopenic due to an increased platelet clearance. In their study Catani et al investigated whether the CD47 pathway played a role in the pathogenesis of human ITP and showed that platelet homeostasis in ITP is abnormally modulated by the CD47 pathway; while the expression of CD47 on platelet surface is normal there is an upmodulation of phagocytosis by macrophages. Such studies are essential in discovering new pathways and targets in the pathogenesis of ITP as they will be instrumental in developing novel effective therapies.

Progress towards successful immunotherapy for elderly patients with acute myeloid leukemia (AML)
Kitawaki et al

Treatment of AML in older patients poses a great challenge to the clinicians due to high rate of therapy related mortality. Antigen-specific immunotherapy as a less toxic intervention may be more beneficial for these patients as a means to eradicate or control residual disease. In this Phase I clinical trial, Kitawaki et al report vaccination of four elderly patients in 2nd or later remission with GM-CSF and Il-4 induced dendritic cells (DC) loaded with autologous apoptotic leukemic cells. They show that the treatment was safe and well tolerated and moreover it induced antileukemic immunity in two of four patients which was also associated with transient disease stabilization. In vivo cross-priming of CD8+ T cells by DCs pulsed with apoptotic leukemic cells in one patient was shown for the first time in an immunotherapy trial. These results are promising but the limited clinical efficacy indicates that further studies are needed to improve vaccine potency or one may have to increase the number of vaccinations to achieve sustained antileukemic immunity.

A powerful target in primary leukemia T-cells: active mTOR
Batista et al

Developing targeted therapies that would work synergistically with conventional chemotherapy will be useful to further improve therapeutic outcome in patients with T-cell ALL. Mammalian target of rapamycin (mTOR), a serine-threonine kinase is an attractive molecule for targeted therapy as it integrates multiple signal transduction pathways. Several studies have already shown the antitumor activity of mTOR inhibitors and their synergistic effect with various chemotherapeutic agents as well as their impact on chemosensitization in various malignancies.

Batista et al have studied the role of mTOR signaling in malignant T cells within the leukemic microenvironment and showed that mTOR signaling is highly activated in these cells and blocking mTOR by Rapamycin or it's analogue significantly inhibited the survival and proliferation of T-ALL cells, even in the presence of protective IL-7. Furthermore, mTOR blockade markedly potentiated the antileukemia effects of Dexamethasone and Doxorubicin, and showed highly synergistic interactions in combination with specific inhibitors of PI3K/Akt and Jak3 signaling. These findings justify the targeting of mTOR signaling in combination with standard chemotherapy and other inhibitors of signaling molecules is a valid strategy in the treatment of T-cell ALL.

Seeking Manuscripts

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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Young Investigators

Committee Moves Forward on Meeting Plans

When you talk to long-time ISEH members and Annual Scientific Meeting attendees, one comment is heard time and time again – ISEH provides more for investigators early in their careers than any other scientific meeting.

This mentoring attitude continues to thrive at ISEH and is being bolstered even more with the formation of the Young Investigators Committee. Committee Chair Shannon McKinney-Freeman, PhD, assistant member, Department of Hematology at St. Jude Children's Research Hospital in Memphis, Tenn., USA, says the committee's recent efforts have focused on the Vancouver meeting.

"In addition to open access to all Annual Scientific Meeting sessions and networking opportunities, young investigators will have three events built solely for them,” McKinney-Freeman shares. "The now-annual Meet the Professor Breakfast is on Saturday morning, and we have already lined up more than half of the professors.”

At the breakfast, young investigator attendees have casual conversation with professors who understand what it takes to succeed in this profession and are willing to share their advice.

The second young investigator event features a panel of experts, whose career paths have taken them outside academia. They will share their insights and answer questions.

"The individuals selected for this panel have chosen to work in science, but are not in the academic research environment,” McKinney-Freeman explains. "They represent industry, publishing and the liberal arts.”

The final young investigator event is the Friday night outing away from the hotel, but within walking distance to maximize attendance. This is a time to continue networking with peers, in a fun and casual setting. The event is supported by STEMCELL Technologies Inc.

Young investigators – be sure to choose this option when you register. You will meet colleagues with whom you will collaborate for years to come.

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Society News

ISEH Leadership: Call for Nominations Opens 3 May
From 3 May to 25 May, ISEH is accepting nominations for the 2011/2012 Board of Directors.

Watch the ISEH website in late April for complete information on how to submit your application for a leadership position. In late May and early June, the Nominations Committee, chaired by Elaine Dzierzak, will review applications and prepare the slate of candidates.

Candidate information then will be posted at iseh.org so that members can educate themselves about the candidates and vote accordingly during the election period, 28 June through 19 July. Results will be posted to the website and elected members will take office at the 40th Annual Scientific Meeting in Vancouver, 25-28 August.

Fellowship Applications Due 10 May

All members are invited to spread the word on the new ISEH Eugene Goldwasser Fellowship, supported by Amgen for an outstanding young investigator in the field of hematology. Requirements for the $50,000 fellowship are posted on the ISEH website and applications will be accepted through 10 May. The award will be presented at the 40th Annual Scientific Meeting in Vancouver.

ISEH is proud to support the advancement of young investigators and thankful to Amgen for its support. Dr. Goldwasser was an early star in our field and dedicated to the mission of ISEH, especially where it related to mentoring young researchers. You can read Dr. Goldwasser's obituary in the April issue of Experimental Hematology.

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News from the Field

Is there a meeting you had hoped to attend? Or, is there a topic you would like ISEH to address? Send your ideas to editor@iseh.org and perhaps our scientific editor can respond.

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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 a few of those members. This issue, meet Grover Bagby.

Grover C. Bagby, Jr., MD, MACP
Professor of Medicine and Molecular Genetics, Oregon Health & Science University and Portland Veterans Administration Medical Center
Portland, Oregon, USA
Chair, ISEH Publications Committee

"Originally, I was going to be a cardiologist,” explains Grover C. Bagby, Jr., MD. "Then, I had a clinical rotation in hematology at the end of my first year of residency.”

That rotation changed his direction, when he realized he truly loved studying blood to learn about patient health. Also, during this rotation, he encountered a young patient diagnosed with acute leukemia. Within 10 days, she had died. This tragic occurrence cemented the fact that no one really knew anything about what caused leukemia at a molecular level. This was the beginning of his life-long quest to study how normal stem cells turn into leukemic stem cells. He completed his second year of residency in internal medicine and then moved on to hematology/oncology training for three years.

"I knew following that hematology rotation that I wanted a lab life in addition to a clinical life,” he offers.

Dr. Bagby went on to serve patients, balancing time both in the clinic and the laboratory, predominantly in the Oregon area. He has seen a great deal of progress in hematology and stem cell research since beginning his first residency in 1969.

"When I first got into this business, we were asking questions about how to understand leukemia so that we could effectively diagnose this disease,” he shares. "By the early 1990s, we had made great strides in experimental hematopoiesis – to the point where scientists like Brian Druker, the inventor of Gleevec®, clearly understood the pathogenesis of chronic myeloid leukemia and could invent drugs that would put patients into durable remission with minimal toxicity.”

Dr. Bagby also pointed to the emergence of molecular biology, gene cloning and high-throughput systems biology as evolutionary steps in experimental hematopoiesis.

Now, later in his career, Dr. Bagby spends more time in the lab at Oregon Health & Science University (OHSU) than in the clinic. His current research focuses on elucidating the function of the Fanconi anemia gene products in maintaining hematopoietic stem cell function and on identifying the pathophysiological mechanisms of clonal evolution in acquired and inherited syndromes of bone marrow failure. His laboratory was the first to identify cytokine hypersensitivity in hematopoietic stem cells with Fanconi gene mutations. Working with investigators in Cincinnati, Dr. Bagby developed an in vitro method of forcing Fanconi stem cells to undergo clonal evolution in vitro. Using systems biology tools and methods of molecular biology and biochemistry, his laboratory has demonstrated that at least some of the Fanconi anemia proteins are multifunctional and that some of their roles in sustaining hematopoiesis are unrelated to their role in protecting cells against genotoxic stress of chemical cross-linking agents. Dr. Bagby's long-term goal is to develop drugs to prevent the development of leukemia in patients at high risk.

"My quest now is to design ways to identify strategies for disease prevention,” he remarks. "Molecular medicine has led to better diagnostics and better therapeutics. It's now time to apply those same tools to disease prevention. I'll take prevention any day.”

His association with ISEH has been long and beneficial. Dr. Bagby has served in numerous leadership positions, including as president in 2000. He also has attended nearly every Annual Scientific Meeting throughout his career.

"I remember attending an ISEH meeting in Basel, Switzerland when it struck me just how different ISEH is from the other societies out there,” he notes. "At ISEH, you can approach people, have a beer and talk science with them. People truly want to interact with one another about science; it is not a place where people just schmooze with the ‘big guys' for political gain or spend all their time at committee meetings.”

Dr. Bagby notes another experience he had very early in his career that set ISEH apart.

"Hal Broxmeyer gave a nice talk on a subject of interest to me at one of our meetings,” he recalls. "I was a fellow; he was a hot shot from Memorial Sloan-Kettering Cancer Center. I saw him in the hallway and approached him to see if I could ask him a few questions. We talked almost an hour and that talk led to a lifelong personal and collegial friendship. There is no way that could have happened at a larger society meeting.”

This year, Dr. Bagby takes on a new leadership role as chair of the ISEH Publications Committee. His publications experience is vast – currently serving as an associate editor for Blood and working with that publisher to create the new eBlood format for descriptive systems biology work. In addition, he has served on the editorial board of numerous publications including multiple terms on Experimental Hematology, has published 125 articles and contributed to nearly 50 books and has reviewed manuscripts for more than 25 different biomedical journals.

With these numerous accomplishments, you might think that Dr. Bagby is all science. However, over the years he has pursued many hobbies, including piano and guitar, woodworking, bicycling and trout fishing. And, he has recently added a few more.

"My number one activity outside of science now is babysitting for my three grandchildren,” he boasts. "That is a new passion. Also, I recently started learning Italian and hope there is a trip to Italy in our very near future.”

 

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