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.
Glypican-3 mediated inhibition of CD26 by TFPI: a novel mechanism in hematopoietic stem cell homing and maintenance, Khurana et al.
This manuscript introduces a novel pathway regulating hematopoietic stem cell (HSC) homing and retention in the bone marrow; both of which are critical events for stem cell function that are directly relevant for the application of stem cell transplantation. HSC homing and retention depend upon the interaction between the CXCL12 chemokine and its receptor, CXCR4. CD26 is a widely expressed, membrane-bound ectopeptidase that cleaves CXCL12 thereby depleting its chemokine activity. In this manuscript, authors identify tissue factor pathway inhibitor (TFPI) as a biological inhibitor of CD26 in both mouse and human hematopoietic and progenitor cells (HPSCs) and thus describe a novel axis involved in HSC homing and engraftment. The authors further identify Glypican-3 (GPC3), a heparan sulphate proteoglycan expressed on mouse and human HSPCs as the receptor for TFPI, in this context; demonstrating that GPC3 is required for TFPI to exert its effects on homing and migration. The investigators also demonstrate that mice lacking GPC3 have a decreased HSC pool in the bone marrow and increased numbers of HSCs in peripheral blood, underscoring a physiological role for GPC3 in modulation of HSC retention in the bone marrow.
Standardization of bleeding assessment in immune thrombocytopenia: report from the International Working Group, Rodeghiero et al.
This report describes a bleeding assessment tool for idiopathic thrombocytopenic purpura (ITP) developed by an international working group, filling an important void in the current ITP literature.
CD30 expression defines a novel subset of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from The International DLBCL Rituximab-CHOP Consortium Program Study, Hu et al.
In this manuscript, the authors study CD30 expression by immunohistochemistry in a large cohort of diffuse large B-cell lymphoma (DLBCL) patients treated with the common therapeutic regimen R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). After dividing patients into training and validation sets, investigators found that CD30 expression was associated with significantly better prognosis compared with the CD30 negative counterpart. These CD30 positive (CD30+) lymphomas have a unique gene expression signature, suggesting that it is a unique molecular subtype. Intriguingly, CD30+ DLBCL that are Epstein-Barr virus positive (EBV+) had significantly worse prognosis. The various analyses were compared to relevant related subtypes of lymphoma to identify unique features. This well- conducted study in a large number of patients helps to further refine existing clinically relevant molecular classification of DLBCL.
Analysis of storage and secretion of von Willebrand factor in blood outgrowth endothelial cells derived from von Willebrand disease patients, Wang et al.
Cellular and molecular basis of von Willebrand disease: studies on blood outgrowth endothelial cells, Starke et al.
These two studies offer insight into the biosynthetic basis and pathogenesis of several types of von Willebrand disease (VWD) using an approach that has significant advantages over studying VWD gene mutations in heterologous cells. The novel "physiological" tool based upon a method of blood outgrowth endothelial cells that is reported in these manuscripts and that clarify the pathophysiology of VWD could be applied to larger populations of patients with all types of the disease.
Combining BCR-ABL1 transcript levels at 3 and 6 months in chronic myeloid leukemia: implications for early intervention strategies, Neelakantan et al.
This paper looks at BCR-ABL transcript monitoring at three and six months during the treatment of chronic myeloid leukemia (CML) in the chronic phase with tyrosine kinase inhibitors. Investigators report data from their analysis of the prognostic value of early transcript reduction on subsequent cytogenetic and complete molecular response as well as survival. In this manuscript authors demonstrate that the copy number at three months is the most important factor and represents a point at which early intervention (i.e., switch in agent) may be warranted and conclude that the copy number at six months is not known to have a large contributing factor. These findings could change the standard of care for molecular monitoring of CML.
Reporters who wish to receive a copy of any of the manuscripts highlighted above or would like to request an interview with the authors may contact Andrea Slesinski at 202-552-4927 or email@example.com
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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