The 48th ASH Annual Meeting in Orlando continued the tradition of focusing the hematology community on the transfer from "bench to bedside" of seminal molecular, cellular, and clinical observations. The E. Donnall Thomas Lecture on Saturday was presented by Dr. E. Richard Stanley. He discussed the importance of colony stimulating factor-1 (CSF-1, also known as M-CSF) in development and disease. The three biologically active isoforms of CSF-1 — a membrane-spanning, cell surface glycoprotein, a secreted glycoprotein, and a secreted proteoglycan — all have separate modes of action. The result is that this important cytokine has a diversity of receptors, cells expressing these receptors, and functions. Perturbations induce multiple disease states, including infections, autoimmune conditions, and malignancy.
The ASH/ASCO Joint Symposium on Sunday, chaired by Drs. Kanti Rai and Gabriel Hortobagyi, addressed the biological and clinical applications of angiogenesis inhibition in malignant diseases. Dr. Lee Ellis discussed the results of trials using inhibitors of vascular endothelial growth factor (VEGF). Dr. Shahin Rafii discussed the role of angiogenesis inhibitors in hematologic conditions, and Dr. Brian Rini discussed the results of trials using anti-angiogenesis agents in solid tumor malignancies.
On Sunday, the inaugural ASH Mentor Awards were announced. This was followed by the Plenary Scientific Session, highlighting the top six abstracts submitted to the meeting. After being introduced by Dr. J. Evan Sadler, Dr. Harmut Weiler from the Blood Research Center of Milwaukee delineated mechanisms, described in abstract #1, for mortality reduction of activated protein C (APC) in sepsis in a mouse model. He reported that the cellular effects of APC can be distinguished from the anticoagulant effects — and that the latter do not appear to be required for the survival benefit in sepsis.
Introduced by Dr. Dieter Hoelzer, Dr. Jacob M. Rowe from Rambam Medical Center in Haifa, Israel, presented abstract #2, the final results of the international ALL trial (MRC UKALL AII/ECOG E2993), which randomized patients with ALL in first complete remission to consolidation with allogeneic stem cell transplant, autologous stem cell transplant, or conventional chemotherapy. He reported superior survival for patients who received allogeneic transplant, but, surprisingly, this benefit was limited to those with standard risk disease. Moreover, survival was superior for all patients in the conventional chemotherapy arm compared to the autologous transplant arm.
After being introduced by Dr. Nancy Andrews, George C. Shaw, a medical student in the lab of Dr. Barry Paw at Brigham and Women’s Hospital in Boston, presented abstract #3. Shaw and colleagues found that the mitoferrin (MFRN) protein was aberrantly spliced and non-functional in children with erythropoietic porphyria (EPP) who did not have the more common mutation in ferrochelatase. These findings underscore the importance of mitochondrial processing in heme synthesis.
Dr. Mark Minden introduced Dr. Richard F. Schlenk from the University of Ulm in Ulm, Germany, who presented abstract #4. Dr. Schlenk’s group examined 871 patients from four separate clinical trials with AML in the “intermediate risk” category with no apparent cytogenetic mutations for presence of several specific molecular markers. They found improved outcomes with the NPMI+/FLT3-ITD and CEBPA mutations in patients less than 48 years of age, indicating that it may be possible to individualize treatment approaches for AML patients.
Abstract #5, presented by Dr. Alessandro M. Vannucchi from the University of Florence, Italy, reported a tight correlation between the proportion of mutant JAK-2 allele in patients with polycythemia rubra vera at diagnosis and major clinical events. Dr. Vannucchi’s abstract was introduced by Dr. Kenneth Kaushansky.
Finally, after being introduced by Dr. Jeffrey I. Weitz, Dr. Henry R. Buller from Academic Medical Center in Amsterdam, The Netherlands, presented abstract #6, the results of the trial conducted by the Van Gogh Investigators comparing once-weekly idraparinux with heparin and vitamin K antagonists for treatment of venous thrombosis. In results that surprised almost everyone, idraparinux was the winner in the DVT trial over heparin and vitamin K antagonists, but the roles were reversed in the PTE trial. The confounding variable was a lower than expected incidence of recurrent thrombosis in patients receiving heparin and vitamin K antagonists. This will require additional studies.
Dr. Aaron Ciechanover from the Israel Institute of Technology, recipient of the 2004 Nobel Prize in Chemistry, delivered the Ham-Wasserman Lecture on Monday. Dr. Ciechanover described how research on protein degradation and the ubiquitin-proteosome system has changed our understanding of multiple basic cellular processes and treatment of diseases such as cancer and neurodegenerative disorders.
The theme of the Presidential Symposium on Tuesday was microRNAs (miRs), naturally-occurring RNAs that regulate gene expression by causing degradation of complementary mRNA. Of note, the 2006 Nobel Prize in Medicine was awarded to Drs. Andrew Fire and Craig Mello for their discovery of gene regulation by this mechanism. Dr. James Dahlberg led off the symposium by describing specific miRs associated with poor-prognosis lymphomas. Dr. Chang-Zheng Chen described the miRs involved in hematopoietic lineage differentiation and maturation. Finally, Dr. Carlo Croce discussed the importance of MiRs in leukemogenesis, highlighting his work on correlations between expression of specific miRs and subtypes of AML. During the Presidential Symposium, Dr. Kanti Rai also presented the William Dameshek Prize for recent outstanding contributions to the field of hematology to Dr. Ricardo Dalla-Favera of the Institute for Cancer Genetics and Herbert Irving Comprehensive Cancer Center at Columbia for his seminal work on lymphomagenesis. The Henry M. Stratton Medal for contributions to hematology over a career was presented to Dr. Jack Hirsh for his work on thrombosis and anti-thrombotic agents.
Finally, the Tuesday afternoon "Special Session on the Basic Science of Hemostasis and Thrombosis," chaired by Drs. Bruce and Barbara Furie and Mortimer Poncz, featured six invited speakers discussing important issues, including the molecular structure of ADAMTS13, the correlation between conformational change of ATIII and differential anticoagulant properties of heparin compounds, the model coagulation reaction system, effects of pre-mRNA splicing on platelet thrombogenicity, the crystal structure of the urokinase-urokinase receptor complex, and the role of gaps between platelets following vascular injury and thrombus stability.
Clearly, the breakthrough science and advances in education showcased at this year’s meeting ran the full gamut of "bench to bedside."
