Issue 3, Volume 127

Cover Figure: Novel MPL and JAK2 mutations in triple-negative MPN. See the article by Cabagnols et al.

WASHINGTON, January 21, 2016 – 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, PhD, and Deputy Editor Nancy Berliner, MD.

Whole-exome sequencing identifies novel MPL and JAK2 mutations in triple-negative myeloproliferative neoplasms

Presence of atypical thrombopoietin receptor (MPL) mutations in triple-negative essential thrombocythemia patients
In two parallel studies in this week's Blood, Milosevic Feenstra et al and Cabagnols et al report the discovery of novel heterogeneous mutations in the MPL and JAK2 genes in 5%-10% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) who are "triple negative," that is, lacking the classical JAK2, MPL, and CALR gene mutations in these diseases. These new genomic findings in PMF and ET are important for future research and clinical practice.

High-dose dexamethasone vs prednisone for treatment of adult immune thrombocytopenia: a prospective multicenter randomized trial
In this issue of Blood, Wei et al report the results of a uniquely large and long-awaited prospective randomized trial of high-dose dexamethasone (HD) versus standard-dose prednisone (PDN) for the treatment of newly diagnosed adult primary immune thrombocytopenia (ITP). HD gives a shorter time to response and a higher rate of initial response, as well as less toxicity, and represents a preferred treatment strategy in the first-line management of ITP.

Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia
In this week's Blood, Thompson and colleagues report their remarkable long-term results of the use of fludarabine, cyclophosphamide, and rituximab (FCR), the gold standard of chemoimmunotherapy for younger patients with previously untreated chronic lymphocytic leukemia (CLL). The study demonstrates a plateau on the survival curves for patients with mutated IGHV, raising the possibility of cure in a subset of patients. These data furnish strong support for clinicians to use FCR as the standard of care. They also reinforce FCR as the reference regimen for comparing the therapeutic efficacy of combinations of novel agents in patients of younger age.

Gnb isoforms control a signaling pathway comprising Rac1 and Plcβ2/3 leading to LFA-1 activation and neutrophil arrest in vivo
Effective elimination of invading microorganisms requires the recruitment and subsequent activation of leukocytes, in which integrins are central components as major adhesion receptors. The activation state of integrins is tightly regulated by intracellular signaling mechanisms termed inside-out signaling, which switches integrins to a high-affinity state. In their study in the current issue of Blood, Block et al provide critical insights into the indispensable role of G protein β-subunit isoforms (Plcβ2/3) in chemokine-induced signaling through Rac1 and phospholipase Cβ2/3, which lead to LFA-1 integrin activation in neutrophils.

Eliminating minimal residual disease as a therapeutic end point: working toward cure for patients with CLL
Assessment of minimal residual disease (MRD) as a surrogate therapeutic end point for progression-free survival is a topic of rapidly growing importance in CLL. In a comprehensive review, Thompson and Wierda highlight available methodologies for detecting MRD and correlations with posttreatment outcomes. They describe the potential utility of MRD to direct individualized therapy and discuss the importance of MRD-negative status as an early indicator of clinical benefit.

How I treat relapsed classical Hodgkin lymphoma after autologous stem cell transplant
In a timely "How I Treat" article, Alinari and Blum summarize the inherent problems and current salvage treatment options for patients with classical Hodgkin lymphoma (cHL) who relapse after autologous stem cell transplantation. The authors also comprehensively review the emerging exciting opportunities offered by drug-antibody conjugates such as brentuximab vedotin and immune-checkpoint inhibitors. Finally, they offer evidence-based recommendations for a patient-tailored approach that will be useful for practicing hematologists managing patients with relapsed cHL.

This week's complete table of contents

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Blood (, 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) (, the world’s largest professional society concerned with the causes and treatment of blood disorders.

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