Current Opinion in Hematology

PURPOSE OF REVIEW: Packed red blood cells (PRBCs) are the most commonly transfused blood products. Preparation of PRBCs requires blood collection from donors, processing, and storage prior to transfusion to recipients. Stored red blood cells (RBCs) undergo structural and metabolic changes collectively known as the storage lesion. RBC extracellular vesicles (sREVs) are released in PRBC units during storage, and are transfused along with intact RBCs into recipients. For several decades, extracellular vesicles have been the focus of intense research, leading to the discovery of a wide variety of endogenous biological properties that may impact numerous physiologic and/or pathologic pathways...

PURPOSE OF REVIEW: Myelofibrosis (MF) is primarily driven by constitutive activation of the Janus kinase/signal transducer of activators of transcription (JAK/STAT) pathway. While JAK inhibitors have shown to alleviate disease symptoms, their disease-modifying effects in MF are limited. The only curative treatment remains allogeneic stem cell transplantation, which can be applied to a minority of patients. As a result, there is a need to explore novel targets in MF to facilitate appropriate drug development and therapeutic pathways...

PURPOSE OF REVIEW: Chediak-Higashi syndrome is a rare autosomal recessive disorder characterized by congenital immunodeficiency, bleeding diathesis, pyogenic infection, partial oculocutaneous albinism, and progressive neurodegeneration. Treatment is hematopoietic stem cell transplantation or bone marrow transplantation; however, this does not treat the neurologic aspect of the disease. Mutations in the lysosomal trafficking regulator (LYST) gene were identified to be causative of Chediak-Higashi, but despite many analyses, there is little functional information about the LYST protein...

PURPOSE OF REVIEW: Inflammation is now recognized as a major regulator of hematopoietic stem cell (HSC) function. Adult hematopoietic stem cells can adaptively modulate hematopoietic output in direct response to acute infection and inflammation. Conversely, prolonged exposure to inflammation can drive impaired HSC function, clonal expansion, and malignant transformation. As compared with adult hematopoiesis, the effects of prenatal inflammation on developing hematopoietic stem cells are understudied...

PURPOSE OF REVIEW: Recent discoveries have provided evidence for mechanistic links between the master regulator of hematopoiesis GATA2 and the key component of interferon and innate immunity signaling pathways, interferon-regulatory factor-8 (IRF8). These links have important implications for the control of myeloid differentiation in physiological and pathological states. RECENT FINDINGS: GATA2 deficiency resulting from loss of the Gata2 -77 enhancer in progenitors triggers an alarm that instigates the transcriptional induction of innate immune signaling and distorts a myeloid differentiation program...

PURPOSE OF REVIEW: The identity of the erythroblastic island (EBI) macrophage (Mϕ) has been under investigation for decades since it was recognized as the first hematopoietic niche 'nursing' terminal erythropoiesis. This review will focus on the current insights to the characteristics and the role of the EBI Mϕ balancing terminal erythropoiesis and granulopoiesis. RECENT FINDINGS: While the EBI has long been known as the niche for erythroid precursors, significant advancements in biology research technologies, including optimization of EBI enrichment protocols, single-cell ribonucleic acid sequencing, and imaging flow cytometry, have recently revealed that granulocytic precursors co-exist in this niche, termed erythromyeloblastic island (EMBI)...

No abstract text is available yet for this article.

PURPOSE OF REVIEW: It is well described that tumor-directed aberrant myelopoiesis contributes to the generation of various myeloid populations with tumor-promoting properties. A growing number of recent studies have revealed the importance of the previously unappreciated roles of erythroid progenitor cells (EPCs) in the context of cancer, bringing the updated concept that altered erythropoiesis also facilitates tumor growth and progression. Better characterization of EPCs may provide attractive therapeutic opportunities...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

PURPOSE OF REVIEW: Natural killer (NK) cells are a type of immune cell that play a crucial role in the defense against cancer and viral infections. The development and maturation of NK cells is a complex process, involving the coordination of various signaling pathways, transcription factors, and epigenetic modifications. In recent years, there has been a growing interest in studying the development of NK cells. In this review, we discuss the field's current understanding of the journey a hematopoietic stem cell takes to become a fully mature NK cell and detail the sequential steps and regulation of conventional NK leukopoiesis in both mice and humans...

PURPOSE OF REVIEW: Granulocyte colony-stimulating factor (G-CSF) is now a standard agent to mobilize hematopoietic stem cells (HSCs) from the bone marrow to circulation. This review introduced mechanistic insights from the aspect of the sympathetic nervous system (SNS). RECENT FINDINGS: Mobilization efficiency is determined by the balance between promotion and suppression pathways critically regulated by the SNS. G-CSF-induced high catecholaminergic tone promotes mobilization by (1) the strong suppression of osteolineage cells as a hematopoietic microenvironment and (2) fibroblast growth factor 23 production from erythroblasts, which inhibits CXCR4 function in HSCs...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

PURPOSE OF REVIEW: Therapies that target the immune system are increasingly used across oncology, including in hematologic malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). While allogeneic transplant has been a key therapy in these cancers, new approaches that target the immune system are being explored including immune checkpoint therapies, antibody-drug conjugates, and cellular therapies. RECENT FINDINGS: This review outlines updates in the preclinical rationale for immune directed therapies in MDS and AML, as well as recent clinical trials exploring these therapies...

PURPOSE OF REVIEW: There have been major advances in our understanding of molecular pathogenesis of myeloid neoplasms, which prompt the updates in the classification of myeloid neoplasms in the fifth edition of World Health Organization Classification (WHO-5) and the new International Consensus Classification (ICC). The purpose of this review is to provide an overview of these two classification systems for myeloid neoplasms. RECENT FINDINGS: The definition, classification, and diagnostic criteria in many myeloid entities have been refined in WHO-5 and ICC with improved understanding of morphology and integration of new genetic findings...

PURPOSE OF REVIEW: Development of hepcidin therapeutics has been a ground-breaking discovery in restoring iron homeostasis in several haematological disorders. The hepcidin mimetic, rusfertide, is in late-stage clinical development for treating polycythemia vera patients with a global phase 3 trial [NCT05210790] currently underway. Rusfertide serves as the first possible noncytoreductive therapeutic option to maintain haematocrit control and avoid phlebotomy in polycythemia vera patients...

PURPOSE OF REVIEW: Two years after the recognition of VEXAS (for Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, we propose an extensive review of the current understanding of VEXAS pathophysiology and therapeutic options. RECENT FINDINGS: Among the nearly 150 articles published about VEXAS, some have provided determinant insights into VEXAS pathophysiology and treatment. Clinical data from retrospective series support the JAK inhibitor ruxolitinib as the most efficient strategy to control inflammation, and interesting results were also described with azacytidine...

PURPOSE OF REVIEW: The aim of this review is to provide a complete perspective of the evidence that led to the three recent new landmarks of myelodysplastic syndromes (MDS) definition and prognostication: the WHO 2022 and International Consensus Classification (ICC) 2022 classification and the Molecular Intermational Prognostic Scoring System (IPSS-M) score. RECENT FINDINGS: The molecular founding lesions of MDS are strongly linked with disease phenotype and prognosis, therefore the genetic assessment have become part of MDS classifications and prognostication...

PURPOSE OF REVIEW: The aim of this study was to provide insight into how novel next-generation sequencing (NGS) techniques are set to revolutionize clinical practice. RECENT FINDINGS: Advances in sequencing technologies have focused on improved capture of mutations and reads and cellular resolution. Both short and long read DNA sequencing technology are being refined and combined in novel ways with other multiomic approaches to gain unprecedented biological insight into disease...