- 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
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
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
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.