The June issue of Experimental Hematology is here!

Explore the latest findings, innovative studies and thought-provoking insights that continue to shape the field!  Read the June Issue on ExpHem. 

Explore this Issue's Lineup:

Inherited disorders of granulopoiesis: understanding pathogenesis to advance new therapies

Patricia Arreba-Tutusaus, Natalia Borbarán-Bravo, Larissa Doll,...Maksim Klimiankou, Karl Welte, Julia Skokowa

Open Access

Rare inherited disorders that disrupt granulopoiesis highlight the essential role of neutrophils in human health. This review examines the pathogenesis of severe congenital enutropenia syndromes and explores how genetically diverse mutations converge on shared clinical outcomes and common pathogenic mechanisms. Moreover, we discuss experimental models and emerging technologies that have advanced our understanding of disease biology and are accelerating the development of potential therapeutic strategies. Read more>

Genetic variation and inflammation intersections: GATA2- and RUNX1-linked mechanisms of blood pathogenesis

Vu L. Tran, Kirby D. Johnson, Emery H. Bresnick

Germline genetic variation can predispose hematopoietic stem and progenitor cells to bone marrow failure and hematologic malignancies. Why conditionally pathogenic (CP) genetic variation is insufficient for pathogenesis is incompletely understood. This review considers how inflammation triggers or amplifies the functional ramifications of CP variation as a blood pathogenic mechanism, with a particular emphasis on GATA2 and RUNX1 transcription factor-linked mechanisms. Read more>

Highlighting the contributions of Professor T. Ray Bradley to ISEH and the field of Experimental Hematology

Ivan Bertoncello, Louise E. Purton, Toshio Suda, Evan Richard Stanley, Susie K. Nilsson

The International Society for Experimental Hematology (ISEH) was established in 1950 to create a forum for the presentation and discussion of preclinical data in experimental hematology. The official journal of ISEH, Experimental Hematology, was formed in 1972, coinciding with the same year that the annual meeting of ISEH was initiated, hosting 85 scientists from 10 different countries in Milwaukee. Our first President was James P. Okunewick, whose research, including mechanisms underpinning graft versus host disease and delineation of the effects of different chemotherapy agents on hematopoietic stem and progenitor cells, made significant contributions to the field. Read more>

Association of infection frequency and incident clonal hematopoiesis of indeterminant potential

Ajibike Lapite, Vernon A. Burk, James DeCuir,...Christie M. Ballantyne, Elizabeth A. Platz, Katherine Y. King

Open Access

Clonal hematopoiesis of indeterminant potential (CHIP) is a malignancy precursor state that has been shown in preclinical models to be accelerated by infection. We leveraged an ongoing epidemiology study to determine the relationship between infection frequency and incident CHIP. CHIP was determined via whole-exome sequencing at two time points. Documented infection was assessed from routinely collected hospital discharge summaries. Participants with ≥ 3 documented infections had an increased odds of incident CHIP, especially large non-DNMT3A CHIP. This study is the first to demonstrate an association between infection and incident CHIP in a general population, highlighting a modifiable risk factor for CHIP. Read more>

Development of hematopoietic stem cell–targeted lipid nanoparticles through lipid composition optimization

Takamasa Hiraki, Keita Yamamoto, Yu-Hsuan Chang,...Mitsuko Ishihara-Sugano, Motohiro Kato, Susumu Goyama

Open Access

Hematopoietic stem cell (HSC)-targeted gene editing holds significant potential for treating hereditary hematopoietic disorders, yet the efficient and safe delivery of gene-editing tools into HSCs remains a critical challenge. Lipid nanoparticles (LNPs) have emerged as a promising platform for nucleic acid delivery; however, achieving high transfection efficiency in HSCs remains challenging. In this study, we developed HSC-targeted LNPs by integrating Bayesian optimization with our functional amino lipids. Read more>

Induced pluripotent stem cell (iPSC)-derived CAR-macrophages: new kids on the block

Fucai Zhu, Zhongfa Chen, Yan Yu,...Guifang Lin, Jing Deng, Qiuhua Yu

Remarkable outcomes of chimeric antigen receptor (CAR)-T cell therapy in treating hematologic malignancies have inspired parallel efforts to harness the potential of other immune cell types for CAR-based immunotherapy. This review explores induced pluripotent stem cells (iPSCs) as an emerging source for generating iPSC-derived CAR-MACs (CAR-iMACs), providing an overview of MACs and their conventional sources. We discussed the advantages of iPSCs and the technical procedures for generating iPSCs and differentiating them into functional CAR-iMACs. Finally, we explored the preclinical and clinical advances in CAR-iMAC therapy. Read more>

Current landscape of mRNA therapeutics for acute myeloid leukemia

Mira Hamed, Olivia Kovecses, Maureen McKeague

Open Access

mRNA therapeutics provide a way to achieve controlled, transient protein expression without altering DNA, making them attractive for diseases like acute myeloid leukemia (AML) where safety and reversibility matter. This Perspective reviews recent progress in delivering mRNA to hematopoietic cells, surveys emerging applications in leukemic reprogramming and cell therapy, and examines the biological and practical barriers that still limit translation. We argue that mRNA is best viewed as an enabling technology integrated into existing treatment strategies, rather than as a stand-alone cytotoxic therapy. Read more>

From image to insight: optimized multiplex staining panel for formalin-fixed, paraffin-embedded mouse bone marrow enables spatial profiling of the hematopoietic niche

Franziska Zell, Katharina Gellrich, Albert Gründer,...Lena Illert, Heike L. Pahl, Hans Felix Staehle

Open Access

Processing murine femora for immunofluorescence staining poses considerable challenges, and a standardized workflow has not yet been systematically described. In this study, we optimized tissue preparation for murine formalin-fixed, paraffin-embedded femur sections and established an efficient multiplex protocol enabling spatial analysis of hematopoietic stem and progenitor cells within the bone marrow niche. Applying this panel to femur sections from Jak2V617F mice, we observed specific alterations in the megakaryocytic niche, underscoring our method’s utility for detecting spatial features relevant to hematopoietic disease. Read more>

Corrigendum to “Recurrent Transcriptional Responses in AML and MDS patients Treated with Decitabine” Experimental Hematology. 2022;111:50-65

Pawan Upadhyay, Jeremy Beales, Nakul M. Shah,...Daniel C. Link, Timothy J. Ley, John S. Welch

Open Access

The authors regret the omission of Figure 8 and of the axis labels from Supplementary Figures E23, E24, E25, E26, and E28 in the published manuscript. Read more>