(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.
Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1 selective pressure in T-lymphocytes, Dubovsky et al.
Ibrutinib, which inhibits B-cell receptor signaling through inhibition of the Bruton’s tyrosine kinase (BTK), has clinical efficacy in a wide range of B-cell malignancies. In this week’s issue of Blood, Dubovsky and colleagues suggest a broader role for the drug in a manuscript demonstrating that ibrutinib also inhibits interleukin-2 inducible kinase (ITK). ITK is a protein required for Th2 cell signaling, and is implicated in infectious, autoimmune, and neoplastic diseases. For example, the microenvironment of chronic lymphocytic leukemia (CLL) is heavily shifted toward Th2 cells, which provides an environment that inhibits anti-tumor immune responses. By modulating the tumor microenvironment, ITK inhibition can increase the efficacy of anti-CLL therapy. The authors also demonstrate that ITK inhibition decreases infection from listeria and leishmania. These results suggest that ibrutinib has unexpectedly broad antitumor and immunomodulatory effects that may offer applicability to a wide range of disorders.
Bone marrow transplantation for thalassemia from alternative related donors: improved outcomes with a new approach, Gaziev et al.
Bone marrow transplantation using alternative donors for the treatment of hemoglobinopathies has been historically difficult with high rates of engraftment failure and severe graft-versus-host disease, ultimately resulting in low disease-free survival. In this week’s issue of Blood, Gaziev and colleagues report transplantation results for thalassemia using alternate related donors, either phenotypically identical or single-antigen mismatched, and itilizing a more intensive preparative regimen. Their results demonstrate that using thie preparative regimen, extending the donor pool to include alternative related donors has outcomes similar to those reported with matched sibling grafts.
Influence of proband's characteristics on the risk of venous thromboembolism in relatives with factor V Leiden or prothrombin G20210A polymorphisms, Bucciarelli et al.
While factor V Leiden (FVL) and PT20210A are common thrombophilic mutations associated with a relatively low risk of thrombosis, first-degree relatives of patients with these mutations have a highly variable risk of venous thromboembolism (VTE). In this week’s issue of Blood, Bucciarelli and colleagues report on a cohort family study of patients with FVL or PT20210A, with at least one family member homozygous for one or the other gene. Surprisingly, the investigators report that family members were more likely to experience VTE when the proband was heterozygous than when the proband was homozygous. Thrombosis was also more common in relatives of patients who suffered previous thrombi. Recognizing the influence of genotype and clinical phenotype on the risk to other family members will help guide management of patients and their families.
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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