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Volume 130, Issue 24

Cover Figure: aPC blocks ischemia reperfusion via modulation of Nlrp3 inflammasome and mTORC1 See the article by Nazir et al.

December 14, 2017 – 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.

 

Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia
In this week ’s plenary paper, Opoka and colleagues report on a randomized, double-blind study of hydroxyurea in sub-Saharan Africa. They demonstrate that hydroxyurea treatment in a region where malaria is endemic does not increase the clinical severity of malaria and reduces sickle cell disease–related adverse events.

SETD2 alterations impair DNA damage recognition and lead to resistance to chemotherapy in leukemia
SETD2is a histone methyltransferase that is mutated in relapsed acute lymphoblastic leukemia and MLL-rearranged leukemia. Mar et al report that SETD2 mutations confer resistance to DNA-damaging agents by impairing DNA damage response and apoptosis from cytotoxic chemotherapy.

Cytoprotective activated protein C averts Nlrp3 inflammasome–induced ischemia-reperfusion injury via mTORC1 inhibition
In a series of elegant series of in vivo studies with mice, Nazir and colleagues demonstrate that activated protein C (aPC) protects from ischemia-reperfusion injury through PAR1 signaling. PAR signaling downstream of aPC blocks inflammasome activation and inhibits mTORC signaling. This modulation of inflammation is independent of the anticoagulant properties of aPC.

In vivo–generated thrombin and plasmin do not activate the complement system in baboons
Keshari and colleagues examined the complex interaction of coagulation and complement in the pathophysiology of sepsis. While previous studies suggested that coagulation proteins can directly activate complement, the investigators report that purified activated coagulation proteases fail to activate complement in vivo in baboons. This finding suggests that sepsis-mediated complement activation is independent of coagulation.

Hematopoietic stem cell transplantation rescues the hematological, immunological, and vascular phenotype in DADA2
Homozygous adenosine deaminase 2 deficiency (DADA2) is a heterogeneous disease associated with autoinflammation, vasculopathy, immunodeficiency, and bone marrow failure. Hashem et al report 100% survival with hematopoietic stem cell transplantation in 14 patients with this disorder, and they demonstrate that it even resolves the vasculitic complications of the disorder.

Gene expression and risk of leukemic transformation in myelodysplasia
Shiozawa and colleagues performed gene expression profiling of 100 patients with myelodysplasia. They define two subtypes characterized by genes related to erythroid/megakaryocytic lineages and genes related to immature progenitor cells (IMPs). The IMP subgroup has significantly shorter survival and contains all the patients who progress to acute leukemia.

Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients
Ixazomib, an oral proteasome inhibitor, is approved in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least 1 prior therapy. Avet-Loiseau and colleagues report that addition of ixazomib overcomes the poor prognosis associated with high-risk cytogenetics.

Chimeric antigen receptor T-cell therapies for multiple myeloma
Mikkilineni and Kochenderfer review the status of chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma, presenting the range of potential antigen targets and results of early clinical trials.

How I treat heavy menstrual bleeding associated with anticoagulants
In the context of 2 clinical vignettes, Boonyawat and colleagues discuss the risks and management of menorrhagia in women undergoing anticoagulant therapy.

 

This week's complete table of contents

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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.

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