(WASHINGTON) – Welcome to “This Week in Blood,” a weekly snapshot of the hottest studies from each week’s issue of Blood, the official journal of the American Society of Hematology (ASH), hand-picked by Blood Editor-in-Chief Bob Löwenberg, MD, and Deputy Editor Nancy Berliner, MD. If you would like a PDF copy of any of the manuscripts highlighted below or would like to request an interview with the author, please email firstname.lastname@example.org.
Toward eliminating HLA class I expression to generate universal cells from allogeneic donors, Torikai et al.
Achieving long-term engraftment of allogeneic cells requires circumventing immune-mediated rejection, a process primarily accomplished by matching for human leukocyte antigen (HLA) expression and/or immunosuppression. Genetic engineering provides an alternative approach to avoid clearance of cells that are recognized as foreign by the recipient. In this week’s issue of Blood, investigators present an approach of genetic editing of allogeneic donor-derived cells to selectively eliminate expression of HLA-A and produce HLA-negative, donor-derived “universal” cells that may be used as an “off-the-shelf” therapy. These findings provide a foundation for a novel strategy whereby cells from one donor can be administered to multiple donors.
SGN-CD33A: a novel CD33-targeting antibody-drug conjugate utilizing a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML, Sutherland et al.
Survival outcomes in patients with acute myeloid leukemia (AML) remain unsatisfactory, and novel treatments are urgently needed. One promising strategy explores antibody-drug conjugates, particularly those targeting CD33. Given the withdrawal of the anti-CD33 conjugate gemtuzumab ozogamicin (GO) from market and lack of clinical activity surrounding a non-conjugated CD33 antibody, there is a need for rapid clinical development of conjugated CD33 antibodies. In this week’s issue of Blood, investigators report that the conjugation process involved in the production of the antibody SGN-CD33A appears to result in more precise, reproducible, and highly potent conjugates. In preclinical testing SGN-CD33A appears more active than GO against a panel of AML cell lines and primary AML cells in vitro as well as in xenotransplantation studies in mice, setting the stage for the clinical development of the agent.
Inositol hexakisphosphate kinase 1 maintains hemostasis in mice by regulating platelet polyphosphate levels, Ghosh et al.
This manuscript appearing in this week’s issue of Blood indicates that inositol pyrophosphates could be precursors of polyphosphate in mammalian cells and suggests new ways of controlling this important factor in hemostasis. Study authors report that inositol hexakisphosphate kinase 1 (IP6K1) knockout mice display lower inorganic polyphosphate levels in platelets and demonstrate for the first time that low platelet polyphosphate leads to lengthened clotting time, altered clot architecture, and protection against pulmonary thromboembolism. This first report demonstrating investigators’ ability to down-regulate polyphosphate in platelets represents a major step forward in understanding the role of this clotting mediator in vivo and underscores an important role for polyphosphate secreted from activated platelets in both hemostasis and thrombosis.
Rituximab prophylaxis prevents corticosteroid-requiring chronic GVHD after allogeneic peripheral blood stem cell transplantation: results of a phase II trial, Cutler et al.
While peritransplant lymphodepletion is currently the only post transplant strategy to prevent chronic graft-versus-host disease (GVHD), this week’s issue of Blood includes a report on the efficacy and safety of another strategy, the use of post-transplant rituximab for B-cell depletion. In the manuscript researchers observe that rituximab prevented the occurrence of steroid-requiring chronic GVHD and that the therapy was safe without severe infusional adverse events. Accordingly, the cumulative incidences of chronic GVHD and systemic corticosteroid-requiring chronic GVHD at two years post transplant were both significantly lower than the corresponding rates in a concurrent control cohort. Several other outcome estimates including overall survival were also better in rituximab-treated subjects. These results, demonstrating that rituximab can prevent severe chronic GVHD after peripheral blood stem cell transplantation, call for additional study via a prospective randomized trial.
Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field of hematology, is available weekly in print and online. Blood is the official journal of the American Society of Hematology (ASH) (www.hematology.org), the world’s largest professional society concerned with the causes and treatment of blood disorders.
ASH’s mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology.
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