- 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 | Xylina Gregg, MD | Josef Prchal, MD
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.
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.