(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 email@example.com.
Caloric restriction modulates Mcl-1 expression and sensitizes lymphomas to BH3 mimetic in mice, Ricci et al.
While it has been proposed that caloric restriction decreases tumorigenesis through glycolysis and a variety of other mechanisms, understanding of how caloric restriction affects response to cancer therapy is still rudimentary. In this week’s issue of Blood, investigators observe in mice with Emu-Myc lymphoma that mild caloric restriction is sufficient to reduce levels of Mcl-1, a pro-survival Bcl-2-family protein, and sensitizes tumors to death by the BH3-mimetic ABT-737. Ricci and colleagues further characterize the mechanism through in vitro studies, demonstrating that cell death resulting from glycolysis inhibition and ABT-737 is independent of the main BH3-only proteins and of p53. These data uncover novel insights that are directly relevant to improving the efficacy of or preventing resistance to cancer therapy.
Genetic loss of SH2B3 in acute lymphoblastic leukemia, Perez-Garcia et al.
The SH2B adaptor protein 3 (SH2B3) gene encodes a negative regulator of cytokine signaling with a critical role in the homeostasis of hematopoietic stem cells and lymphoid progenitors. In this week’s issue of Blood, Perez-Garcia and colleagues present the first report of germline homozygous mutations of SH2B3 in two siblings with acute lymphocytic leukemia (ALL) and autoimmune-like disorders. The manuscript further reinforces the importance of SH2B3 in the regulation of normal hematopoiesis and stem cells, presenting functional data on the consequences of this genetic mutation on increased B-cell and T-cell signaling and the acceleration of ALL onset in an animal model. These data demonstrate a tumor suppressor role for SH2B3 in the pathogenesis of ALL and highlight a possible link between genetic predisposition factors in the pathogenesis of autoimmunity and leukemogenesis.
PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma, Richardson et al.
The oral pan-deacetylase inhibitor Panobinostat works with bortezomib to inhibit both the aggresome and proteasome pathways in preclinical studies. In a manuscript published this week in Blood, investigators demonstrate significant response rates with panobinostat in multiple myeloma patients considered refractory to bortezomib, even in those who progressed while on bortezomib-based therapy. Among 55 heavily pretreated patients, the overall response rate was 34.5 percent, demonstrating that panobinostat, when combined with bortezomib and dexamethasone, can recapture responses in heavily pretreated, bortezomib-refractory multiple myeloma patients.
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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