The Hematologist

March April 2009 Vol 6 Issue 2

March-April 2009, Volume 6, Issue 2

Features

  • Hemoglobin’s Holy GrailMarch 01, 2009 | Charles Parker, MD, Editor-in-Chief

    At the genetic level, sickle cell disease is unambiguous, resulting from mutation of a single nucleotide (A→G) that introduces an amino acid substitution (valine for glutamic acid) in the β subunit of hemoglobin. At the clinical level, however, the disease is phenotypically diverse, ranging from asymptomatic to debilitating. An important determinant of clinical severity is the patient's level of fetal hemoglobin (HbF, α 2 γ 2 ) as the γ subunit of HbF competes with sickle-β for binding to the α chain.

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Diffusion

  • A Picture is Worth a Thousand WordsMarch 01, 2009 | Nelson Chao, MD, MBA

    That is a truism if there ever was one. The field of stem cells, not just hematopoietic stem cells, is defined by the actual pluripotent or multipotent cells and the necessary niches in which they reside. Elegant experiments with Drosophila melanogaster, Caenorhabditis elegans, zebrafish, and other organisms clearly demonstrated the importance of a single nurse cell (a specialized cell in Drosophila that contributes to the formation of oocytes and acts as the niche) in determining self-renewal and differentiation of the stem cells.

  • Breaking the Barrier: Molecular Basis of the Blood–Brain BarrierMarch 01, 2009

    That vital organ, the brain, is protected by the blood-brain barrier (BBB), which is composed of both a physical barrier formed by tight junctions between brain capillary endothelial cells (ECs) and a selective active transport system, including a multiple drug resistance transport system that precludes some drugs and chemicals from entering the brain.

  • Resistance is Not FutileMarch 01, 2009 | Jerald Radich, MD

    Relapse is the primary hurdle of leukemia therapy. This remains true despite more complex therapy, more aggressive treatment schedules, and newer, targeted therapy. In acute leukemia (AML and ALL), most patients will obtain a first remission, but many will subsequently relapse. Once relapse occurs, cure is difficult, if not impossible, with chemotherapy alone.

  • Sequence of Therapy in Leukemia: An Ever-Recurring Question Now Relevant to CLLMarch 01, 2009 | John C. Byrd, MD

    The initial use of chemotherapy for CLL has evolved over the past 15 years from alkylator-based monotherapy to fludarabine and then to fludarabine/cyclophosphamide (FC) based upon well-designed randomized phase III studies demonstrating improved overall response (OR), complete remission (CR), and progression-free survival (PFS) with successive treatment regimens.

  • The GVL Effect RevisitedMarch 01, 2009 | Gérard Socié, MD, PhD

    Immune-mediated eradication of leukemias, the so-called graft-versus-leukemia (GVL) effect, is a major beneficial effect observed after allogeneic hematopoietic cell transplantation (HCT). Patients with graft-versus-host disease (GVHD) (especially chronic GVHD) have a lower risk of relapse compared with patients without GVHD.

  • The Paradox of the Anti-Inflammatory ImmunoglobulinMarch 01, 2009 | Pete Lollar, MD

    In 1890, von Behring and Kitasato described the presence of "antitoxins," which we now call antitoxin antibodies, in the sera of animals immunized with preparations of diphtheria or tetanus toxin. 1 The following year von Behring successfully treated a child with diphtheria with a preparation of the antitoxin antibody and in 1904 founded Behringwerke to commercialize the use of passive and active immunization to treat infectious diseases.

  • Therapeutic Potential of Targeting the ImmunoproteasomeMarch 01, 2009 | Kenneth C. Anderson, MD

    Kuhn and colleagues report on the novel strategy of targeting the immunoproteasome to overcome bortezomib resistance on the one hand, and avoid side effects on the other. The core proteasome (20S) protease complex is composed of α and β subunits; the β1, β2, and β5 subunits mediate caspase-like (C-L), trypsin-like (T-L), and chymotrypsin-like (CT-L) activities.

  • There Goes the Neighborhood: The Leukemic Microenvironment Co-Opts Normal Hematopoietic Progenitor Cells From Their Supportive Marrow NicheMarch 01, 2009 | Michael Linenberger, MD

    Cancer cells expand and metastasize as a result of their intrinsic genetic and epigenetic alterations and complex interactions within the normal tissue and tumor microenvironmental niches. Leukemias arise within the marrow, which is organized into specialized niches that regulate normal hematopoietic progenitor cell (HPC) homing, lodgment, maintenance, proliferation, and differentiation.

  • Unmasking the Serine Protease TMPRSS6: Its Role in Regulating Iron MetabolismMarch 01, 2009 | Gregory M. Vercellotti, MD

    At the 2007 ASH annual meeting in Atlanta, Ernest Beutler was scheduled to present another amazing hematologic breakthrough during the plenary session. Because of his ill health, his son Bruce presented pictures of a semi-hairless mouse with anemia, microcytosis, iron deficiency, and high hepatic levels of hepcidin mRNA transcripts. 1

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Ask the Hematologist

  • Ask the Hematologist March-April 2009March 01, 2009

    A 22-year-old woman is referred for persistent elevated platelet count. She is well and her past history is negative. Physical examination is notable for splenomegaly (palpable 2 cm below the costal arch). Current CBC shows platelet count of 900,000/μl with normal hematocrit and WBC count. The diagnostic workup, including bone marrow histology, was consistent with JAK2V617F mutated essential thrombocythemia (ET). Counseling for pregnancy planning is also requested.

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Profiles

  • William Williams: Writing "The Book" on HematologyMarch 01, 2009 | Victor Yazbeck, MD

    William J. Williams, MD, has left a unique stamp on the field of hematology through his exemplary patient care and research, and he also wrote “the book” on the field, editing what became for most of the 1970s and 80s one of the two most familiar English-language hematology textbooks.

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President's Column

  • Moving Beyond the “A” in ASHMarch 01, 2009 | Nancy Berliner, MD

    I hope that by this time in the New Year your resolutions have not completely waned and that you are still inspired by the possibilities for great things in 2009. I continue to bask in the glow of our historical inauguration and its promise for renewed collaboration and civil discourse. The unprecedented national and international media coverage of the inauguration underscores again how small our world has become, and so it seems especially appropriate that this year at ASH should be marked by new global initiatives that will strengthen our ties with the international hematology community.

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Letters to the Editor

  • Poorer Patient Care: A Consequence of Increased Co-Pays and DeductiblesMarch 01, 2009

    A greater part of the cost of medical care has shifted from insurance companies to the individual patient because of increases in co-pays and deductibles. A consequence of these increases is a change in patient behavior, which is rarely to his or her medical advantage.

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News and Reports

  • 2009 EHA-ASH Research Exchange Awards Presented to Drs. Freda Passam and Carmen SchweighoferMarch 01, 2009 | Willem Fibbe, MD, PhD

    In 2006, the European Society of Hematology (EHA) and ASH introduced the EHA-ASH Research Exchange Award, a groundbreaking award for both clinical and laboratory-based researchers in training or early in their careers. This award offers them an opportunity to experience research in a different environment and to establish new collaborations with established scientists from around the world.

  • ASH Career Timelines: Helping Trainees Meet Their MilestonesMarch 01, 2009 | Dale Bixby, MD, PhD

    Training to become an effective clinician and researcher in hematology has become an extremely lengthy and complex activity. Currently, 1,348 Associate members of ASH include physicians enrolled in programs leading to certification in multiple hematology-related clinical disciplines as well as non-physicians enrolled in pre- and post-doctoral research training programs.

  • Translational Research Training in Hematology Program Debuts in 2010March 01, 2009 | Linda J. Burns, MD

    In response to increasing demand from European researchers to focus on translational research, ASH and the European Hematology Association (EHA) have collaborated to create the Translational Research Training in Hematology (TRTH) program. The program will provide promising translational investigators an opportunity to undertake intensive training in the pathogenesis, diagnostics, and experimental treatment of hematologic disorders from some of the most recognized names in the field.

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