Volume 133, Issue 25



June 20, 2019 – 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.

Cover Figure: An antitumor strategy via targeting vascular tumor integrity through platelet GPVI. See the article by Volz et al.

Calreticulin mutants as oncogenic rogue chaperones for TpoR and traffic-defective pathogenic TpoR mutants
Exome sequencing has demonstrated that calreticulin (CALR) gene mutations are important gain-of-function myeloproliferative neoplasm driver mutations. This work reveals that mutated CALRs behave as rogue chaperones for the thrombopoietin receptor (TpoR) and traffic-defective TpoR mutants, a function required for oncogenic effects.

Inhibition of platelet GPVI induces intratumor hemorrhage and increases efficacy of chemotherapy in mice
The investigators identify platelet glycoprotein VI (GPVI) as a key regulator of vascular integrity, specifically in growing tumors, and establish a potential antitumor strategy by interfering with the ability of platelets to maintain vascular integrity within the tumor microenvironment.

Prognostic impact of circulating tumor DNA status post–allogeneic hematopoietic stem cell transplantation in AML and MDS
The investigators demonstrate that circulating tumor DNA in the serum can be used for minimal residual disease (MRD) assessment in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic cell transplantation and that it offers a tool to monitor MRD without the burden of frequent bone marrow punctures.

Familial predisposition to TP53/complex karyotype MDS and leukemia in DNA repair-deficient xeroderma pigmentosum


ERCC6L2 defines a novel entity within inherited acute myeloid leukemia
In 2 accompanying articles, the authors find that homozygous germline founder mutations in genes encoding nucleotide excision repair proteins confer risk for leukemias characterized by TP53 mutations.

Low vs high hemoglobin trigger for transfusion in vascular surgery: a randomized clinical feasibility trial
In this study, patients undergoing vascular surgery were randomized to receive a red blood cell transfusion when their hemoglobin was <9.7 g/dL (high-transfusion–trigger group) or <8.0 g/dL (low-trigger group). The results show the importance of optimizing the integration of blood transfusion into clinical care to enhance treatment outcome.

Activation of hedgehog signaling associates with early disease progression in chronic lymphocytic leukemia
This study shows that a large proportion of patients with chronic lymphocytic leukemia harbor mutations in genes involved in the hedgehog (Hh) pathway, resulting in activated Hh signaling. Hh signaling is associated with early disease progression and enhanced sensitivity to inhibition of GLI1.

Stimulated release of intraluminal vesicles from Weibel-Palade bodies
This work describes the presence of intraluminal vesicles in Weibel-Palade bodies for the first time. Weibel-Palade bodies are a prominent storage compartment for hemostatic and inflammatory cargo in endothelial cells.

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