The Hematologist

July August 2009 Vol 6 Issue 4

July-August 2009, Volume 6, Issue 4

Features

  • Mantle-Cell Lymphoma: Not Always AggressiveJuly 01, 2009 | John C. Byrd, MD

    For many years prior to immunophenotyping and detailed molecular characterization, mantle-cell lymphoma was identified as an indolent lymphoma and treated according to the paradigm of treatment intervention only when symptoms develop. The watch-and-wait paradigm for treatment of low-grade lymphoma is derived from many clinical trials demonstrating no benefit in terms of survival with early intervention.

  • What You Should Know About the Patient-Centered Medical HomeJuly 01, 2009 | Bradford Schwartz, MD

    The Patient-Centered Medical Home (PCMH) is a model of team-based care designed to provide continuous and coordinated care throughout a patient's lifetime. Essentially, the model attempts to re-establish the primary-care physician's (PCP) traditional roles of advocate and coordinator of health-care activities, such that the physician's practice becomes the patient's "home" for medical care.

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Diffusion

  • The Wasteland of Relapsed Adult ALLJuly 11, 2009 | Jerald Radich, MD

    The advance of therapy for pediatric ALL is a success story that oncology can revel in; it also places the bar very high for the rest of the oncology landscape. Whereas pediatric ALL therapy can cure upward of 80 percent of patients, success in adult ALL is stuck at a rate of ~40 percent.

  • Adult ALL: To Transplant or Not To Transplant: Is That the Question?July 01, 2009 | Jerald Radich, MD

    ALL is a great success story for pediatric hematology. So effective is the treatment of childhood ALL that protocols are actually examining reducing therapy for selected subgroups. Meanwhile, in the adult world gains are incremental. Most adult ALL patients will go into a complete remission (CR), but most will relapse. Once relapse occurs, the chance of long-term survival with chemotherapy is minute.

  • Does MicroRNA-150 Determine Commitment to Blood Cell Lineages?July 01, 2009

    MicroRNAs (miRNAs) are short, non-coding, single-stranded RNA molecules of 22 nucleotides that regulate an estimated 30 percent of mammalian genes, mostly by repressing target gene expression via either translational repression or mRNA degradation. MiRNAs are involved in a wide variety of normal and pathological cellular processes, including tumorogenesis. There is growing evidence that miRNAs also regulate mammalian hematopoiesis and that some miRNAs are specific for hematopoietic lineages.

  • Human Oral Chronic GVHD: A Th1 Disease?July 01, 2009 | Gérard Socié, MD, PhD

    Chronic graft-versus-host disease (cGVHD) is one, if not the major, long-term complication of allogeneic hematopoietic stem cell transplantation. Most of the knowledge of the pathophysiology of cGVHD has been derived from mouse models. However, experimental models of cGVHD pathogenesis poorly describe the clinical spectrum of the disease.

  • KINDLIN3 Ties Together a Relationship Between Recurrent Infections, Bleeding, and OsteopetrosisJuly 01, 2009 | Pete Lollar, MD

    Three leukocyte adhesion deficiency (LAD) disorders have been described. The most common, type I, is associated with recurrent infections and is due to absent β 2 integrin (CD18) on leukocytes. Subjects present with delayed umbilical cord separation, frequent bacterial infections, and marked leukocytosis. The least common, LAD-II, is characterized by deficient or absent protein fucosylation and mild neutrophil dysfunction, but severe physical and mental developmental problems.

  • Linking HDAC and Proteasome InhibitionJuly 01, 2009 | Steven Grant, MD

    Histone deacetylase inhibitors (HDACIs), including vorinostat, which has recently been approved for the treatment of cutaneous T-cell lymphoma, represent prototypes of agents that act through epigenetic mechanisms. It has generally been assumed that such agents act by acetylating the positively charged histone tails of nucleosomes, leading to a more relaxed chromatin structure and transcription of genes that induce cell differentiation or death.

  • Predicting Response to Proteasome Inhibitor TherapyJuly 01, 2009 | Kenneth C. Anderson, MD

    Cenci and colleagues from Milan reported on the relationship between proteasome expression and workload within tumor cells and their response to proteasome inhibitor (PI) therapy. Specifically, they characterized multiple myeloma (MM) cell lines and showed that those with low proteasome expression and higher workloads were more sensitive to PI than those with higher proteasome expression and lower workloads, which are resistant to PI treatment.

  • Roadwork InfrastructureJuly 01, 2009 | Nelson Chao, MD, MBA

    The bone marrow is an intricate organ that produces the cellular elements found in the blood. The interplay between the hematopoietic stem cells (HSCs) and the cells of its niche has been an area of intense research. The balance between the HSCs, osteoblasts, osteoclasts, osteoMACS (macrophages lining the periosteum), endothelial cells, and reticular cells has been suggested to impact cellular output.

  • Survival of the Fittest: Another Evolutionary Ploy of the Red Cell to Avoid Malaria InfectionJuly 01, 2009 | Gregory M. Vercellotti, MD

    This year is the bicentennial of the birth of Charles Darwin and the sesquicentennial of the publication of On the Origin of Species. For thousands of years the principles of evolution have been played out in the minuet between the malaria parasite and the red blood cell. Survival of the human species has depended upon genetic resistance to malaria across the globe. Evolutionary anti-malarial strategies have included inhibition of intracellular growth, release of mature merozoites or entry into the red cell, promotion of phagocytosis and immune clearance of infected cells, and prevention of vascular or blood cell adherence of infected red cells.

  • The Emerging Role of Prostaglandin E2 in Regulating Stem Cell FunctionJuly 01, 2009

    Hematopoietic stem cell (HSC) transplantation is used to treat a variety of malignant and benign hematologic disorders. Many efforts over the years have been directed at enhancing HSCs to make this process safer, more efficient, and more widely available. Previous observations indicate that Wnt signaling and prostaglandin (PG) E 2 activation pathways regulate HSC survival and self-renewal. Two recent studies shed new light on these mechanisms and their potential utility as modifiable targets for therapeutic applications.

  • What Was Old Is New AgainJuly 01, 2009 | Charles Parker, MD, Editor-in-Chief

    The chronic intravascular hemolysis that is the hallmark clinical manifestation of paroxysmal nocturnal hemoglobinuria (PNH) is mediated by the alternative pathway of complement (APC) (Figure 1). Because the antibody-independent APC is primed for attack at all times, elaborate mechanisms for self-recognition and protection of the host against complement-mediated injury have evolved.

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Ask the Hematologist

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Profiles

  • Ralph O. Wallerstein, MD (1922-2009)July 01, 2009 | Stanley Schrier, MD

    In the fall of 1959, at the almost-regular meetings of the Bay Area Blood Club in San Francisco, I first met Ralph Wallerstein. I was a very new instructor in hematology at Stanford, and Ralph was arguably the leading hematologist in the Bay Area with the academic rank of clinical professor in medicine and laboratory medicine at the University of California, San Francisco (UCSF).

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President's Column

  • The Ongoing COI DebateJuly 01, 2009 | Nancy Berliner, MD

    The recent release of the Institute of Medicine's (IOM) report on "Conflict of Interest in Medical Research, Education, and Practice" has once again thrust the issues surrounding actual or potential conflicts of interest (COI) between the pharmaceutical industry and medical societies such as ASH into the spotlight of public scrutiny and debate.

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Op-Ed

  • Hematology and Goliath: Ensuring the Future of Benign Hematology in a World of Combined Hematology-Oncology FellowshipsJuly 01, 2009 | Alison Loren, MD, MS

    During the Training Program Directors' meeting at the 2008 ASH Annual Meeting, an anecdote was told about an "unnamed Hematology/Oncology program in the Northeast" that is internationally renowned for non-malignant hematology. Even at this institution, the presenter noted, where hematology features prominently in research, education, and patient care, a "benign" hematologist is produced at the rate of just one graduate every one to two years, from a class of six to eight fellows per year.

  • The Physician as a Scientist and a HealerJuly 01, 2009 | David S. Rosenthal, MD

    What happened to the time when a physician, hematologist or otherwise, was a researcher, clinician, teacher, and healer? As medical practice has become more complex, have we become too focused on treating disease and not the whole person? Have we incorporated both qualitative research, such as quality-of-life and survivorship findings, and quantitative research, such as tumor models, into standard care? To achieve the goal of best managing patients' symptoms, it seems important to address both quantitative and qualitative measures.

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Letters to the Editor

  • Hematology and GlycobiologyJuly 16, 2009

    Earlier this year, the NHLBI convened a working group workshop on the roles of glycans in hemostasis, inflammation, and vascular biology. The Working Group Report has just been published in Glycobiology.

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News and Reports

  • The Evolution of Hematology.orgAugust 12, 2009

    The new Hematology.org includes a vibrant, dynamic design and new features that allow users to easily find what they need in as few clicks as possible. The site is now powered by a Web content management system that helps streamline the Web content development and delivery process and allows for automation of certain functions that were not possible under the previous static structure of the site.

  • ASH Kicks Off 50th Anniversary: Notes from the Editor-in-ChiefJuly 09, 2009 | Peter Emanuel, MD

    Next year marks the 50th anniversary of the American Society of Hematology. In the months leading up to 2008, you will hear about the many ways ASH is celebrating its 50th anniversary. This all culminates with the annual meeting celebration in San Francisco in 2008.

  • 2009 MMSAP ParticipantsJuly 01, 2009

    The Minority Medical Student Award Program (MMSAP) encourages minority medical students to pursue an interest in hematology research. For an eight- to 12-week period, MMSAP participants will work closely with their mentors on a hematology-related research project.

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