- A Role for TET2 Dysregulation in Myeloid MalignanciesMarch 01, 2011 | Steven Grant, MD
Aberrant methylation of DNA, particularly hypermethylation of tumor suppressor genes, occurs frequently in many cancers, including hematopoietic malignancies. This has prompted the development of agents capable of reversing hypermethylation, such as DNA methyltransferase inhibitors. These agents have yielded encouraging results both alone and in combination with other epigenetic agents (e.g., histone deacetlyase inhibitors) in patients with myelodysplastic syndrome (MDS) and some acute leukemias.
- Antiphospholipid Antibodies Do NO WrongMarch 01, 2011 | Robert Flaumenhaft, MD, PhD
The underlying molecular events responsible for antiphospholipid antibody syndrome (APS) have been difficult to pinpoint. Characterization of causative antibodies has demonstrated that they are not actually directed at phospholipids, but rather directed at plasma proteins that bind phospholipids. β2-glycoprotein I (β2-GPI) is an important antigen in this regard, but despite its high plasma concentration and central role in APS, the function of β2-GPI in normal physiology remains poorly defined.
- Clinical Anti-Myeloma Activity of AminobisphosphonatesMarch 01, 2011 | Kenneth C. Anderson, MD
Bisphosphonates have demonstrated an ability to reduce skeletal-related events (SRE), including bone pain, pathologic fracture, spinal cord compression, and need for radiation to bone. As approximately 80 percent of patients with multiple myeloma (MM) have bone disease, the use of bisphosphonates has transformed the paradigm for supportive care in MM.
- CT Scans in Response and Follow-Up Assessment of CLL: Can We Eliminate Their Use?March 01, 2011 | John C. Byrd, MD
Chronic lymphocytic leukemia (CLL) is a disease characterized by blood lymphocytosis, cytopenias, bone marrow infiltration, lymph node enlargement, and hepatosplenomegaly. Prior to the availability of modern imaging studies, the Rai or Binet Staging systems employed a routine blood test and physical exam to predict patient outcomes at diagnosis.
- Gene Therapy for Wiskott-Aldrich Syndrome: Benefits and RisksMarch 01, 2011 | Diane Krause, MD, PhD
An international team headed by Dr. Christoph Klein in Germany has reported clinical improvement after gene therapy in two children with Wiskott-Aldrich Syndrome (WAS), a disease caused by mutation of the gene encoding Wiskott Aldrich syndrome protein (WASp). In patients with this condition, the lack of functional WASp, which plays a critical role in actin polymerization in blood cells, leads to thrombocytopenia as well as immunodeficiency with recurrent infections and a tendency toward development of autoimmune diseases.
- Is There a Path to Quality of Life for Elderly Patients Treated for Myeloma?March 01, 2011 | Xavier Leleu, MD, PhD
The treatment of elderly patients with newly diagnosed symptomatic multiple myeloma has improved since the era of melphalan plus prednisone, the standard treatment for more than 30 years. Current regimens still include melphalan plus prednisone as a backbone for combination regimens that contain newer agents, such as bortezomib, lenalidomide, or thalidomide therapy. Despite remarkable response rates and survival benefits, none of these combinations has freed patients and physicians from the anxiety of various side effects. Aside from constipation and somnolence, thalidomide shares thromboembolic events and fatigue with lenalidomide, and peripheral neuropathy with bortezomib.
- Membrane Phospholipid Scrambling by TMEM16FMarch 01, 2011 | Pete Lollar, MD
The plasma membrane of animal cells contains a phospholipid bilayer; the outer leaflet largely contains phosphatidylcholine and sphingomyelin and the inner leaflet is mainly composed of phosphatidylserine (PS) and phosphatidylethanolamine (PE). This lipid asymmetry is maintained by an ATP-dependent enzyme called the aminophospholipid translocase.
- Not Too Little, Not Too Much, Just the Right Amount of Hepcidin Can Limit Iron Overload in β-Thalassemic MiceMarch 01, 2011 | Gregory M. Vercellotti, MD
Remarkable advances in the care of β-thalassemic patients over the past 40 years have prolonged lives and prevented organ dysfunction due to iron overload through the use of parenteral and oral iron chelators. Iron overload occurs in β-thalassemia because ineffective erythropoiesis and frequent RBC transfusions over-enhance iron absorption.
- Take This One for a Test Drive: It Looks Like a HITMarch 01, 2011 | Margaret V. Ragni, MD, MPH
Heparin-induced thrombocytopenia (HIT) is a thrombotic disorder, occurring in 3 percent or more of individuals exposed to heparin, in which antibodies to platelet factor 4-glycosaminoglycan complexes form on platelet surfaces, leading to thrombi, which can be life-threatening. Diagnosis of this disorder can be difficult because the clinical picture may be confusing and assays are limited by poor specificity and lack of availability in real time.
- The Flavors of MPNs: Is STAT1 the Key Ingredient?March 01, 2011 | Jason Gotlib, MD, MS
The Flavors of MPNs Is STAT1 the Key Ingredient?Dr. Gotlib indicated no relevant conflicts of interest. Chen E, Beer PA, Godfrey AL, et al. Distinct clinical phenotypes associated with JAK2V617F reflect differential STAT 1 signaling. Cancer Cell. 2010 18 524
- Turning Over the Rotting Log in Del(5q) MyelodysplasiaMarch 01, 2011 | David P. Steensma, MD
The immunomodulatory drug lenalidomide can induce striking hematologic and cytogenetic responses in patients with myelodysplastic syndromes (MDS), especially among patients whose clonal cells bear a somatic deletion of the long arm of chromosome 5q (del(5q)). Unfortunately, most patients whose cytopenias and burden of clonal cells improve during lenalidomide therapy will relapse within three years - including the approximately 45 percent of patients with lower-risk del(5q) MDS who achieve a complete cytogenetic remission.