Issue Archive

Hematologists have long been fascinated by how platelet production occurs, and our understanding continues to evolve as technology advances and as more and more genetic causes for thrombocytopenia are discovered. In this Review Series on megakaryopoiesis and platelet production edited by Associate Editor John Crispino, experts in the field discuss the latest insights into megakaryopoiesis in fetal and adult life, the varied roles that megakaryocytes are now recognized to play, the mechanics of platelet creation, and how all of this new knowledge underpins clinical disorders requiring diagnosis and management.

Hematologists have long been fascinated by how platelet production occurs, and our understanding continues to evolve as technology advances and as more and more genetic causes for thrombocytopenia are discovered. In this Review Series on megakaryopoiesis and platelet production edited by Associate Editor John Crispino, experts in the field discuss the latest insights into megakaryopoiesis in fetal and adult life, the varied roles that megakaryocytes are now recognized to play, the mechanics of platelet creation, and how all of this new knowledge underpins clinical disorders requiring diagnosis and management.

Hematologists have long been fascinated by how platelet production occurs, and our understanding continues to evolve as technology advances and as more and more genetic causes for thrombocytopenia are discovered. In this Review Series on megakaryopoiesis and platelet production edited by Associate Editor John Crispino, experts in the field discuss the latest insights into megakaryopoiesis in fetal and adult life, the varied roles that megakaryocytes are now recognized to play, the mechanics of platelet creation, and how all of this new knowledge underpins clinical disorders requiring diagnosis and management.

Hematologists have long been fascinated by how platelet production occurs, and our understanding continues to evolve as technology advances and as more and more genetic causes for thrombocytopenia are discovered. In this Review Series on megakaryopoiesis and platelet production edited by Associate Editor John Crispino, experts in the field discuss the latest insights into megakaryopoiesis in fetal and adult life, the varied roles that megakaryocytes are now recognized to play, the mechanics of platelet creation, and how all of this new knowledge underpins clinical disorders requiring diagnosis and management.

Hematologists have long been fascinated by how platelet production occurs, and our understanding continues to evolve as technology advances and as more and more genetic causes for thrombocytopenia are discovered. In this Review Series on megakaryopoiesis and platelet production edited by Associate Editor John Crispino, experts in the field discuss the latest insights into megakaryopoiesis in fetal and adult life, the varied roles that megakaryocytes are now recognized to play, the mechanics of platelet creation, and how all of this new knowledge underpins clinical disorders requiring diagnosis and management.

Ibrutinib and venetoclax are 2 first-in-class novel, non-DNA-damaging anticancer drugs that have each changed outcomes for patients with chronic lymphocytic leukemia (CLL). Tam and colleagues report on a large multicenter phase 2 trial of a fixed duration (15 cycles) of the 2 drugs in combination for previously untreated patients. While longer follow up and phase 3 trials are needed, the 55% complete remission rate, high rates of negativity for minimal residual disease, acceptable safety profile, and few relapses or deaths after 2 years indicate strong promise for this once-daily oral regimen.

The therapeutic potential of monoclonal antibodies to block “don’t eat me” signaling by malignant cells in the tumor microenvironment is rapidly emerging. Cao and colleagues report on a novel and clinically amenable way to prime phagocytes in vivo to enhance the anticancer effect of macrophage checkpoint inhibition. Through direct effects on macrophages, subtoxic doses of paclitaxel synergise potently with anti-CD47 therapy to clear resistant lymphomas in murine models.

Central nervous system (CNS) relapse is a contributor to poor outcomes in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Fernández-Sevilla et al provide clinical and experimental evidence that BMP4 expression levels in leukemia cells could be a useful biomarker to identify children with poor outcome in the low/intermediate risk groups of BCP-ALL. The authors further show in preclinical models that targeting BMP4 has therapeutic potential to prevent or treat leukemic CNS disease.

The release of von Willebrand factor (VWF) into the blood controls platelet adhesion and aggregation. Zeng and colleagues used cryo-electron microscopy to reveal how VWF tubule formation is initiated by a pH-sensing homodimer of the propeptide in a multistep process. From this procedure, they showed how clinical Type 2A von Willebrand disease mutations disrupt this process, leading to diminished VWF multimers in plasma, and how these defects could potentially be rectified.

Idiopathic pneumonia syndrome (IPS) remains a serious complication after allogeneic hematopoietic stem cell transplant (HSCT), causing respiratory failure and death. Lee et al identified aryl hydrocarbon receptor (AHR) to be a critical inflammation checkpoint in lung epithelium, mediating suppression of cytokine-induced activator protein-1 family gene expression. In an in vivo model of IPS after HSCT, the authors demonstrated that pharmacological stimulation of AHR reduces IPS, suggesting a strategy for future clinical exploration.