The February issue of Experimental Hematology is here!

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

Explore this Issue's Lineup:

Malignant Hematopoiesis

Germline heterozygous SH2B3 p.Glu78Lys variant: a three-patient case series with myeloproliferative neoplasms

Giovanni Iaquinta, Alessandro Laganà, Anna Tamburini,...Emanuele Savino, Massimo Breccia, Paola Grammatico

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We report on a rare heterozygous germline SH2B3 (c.232G>A; p.Glu78Lys) in three patients with myeloproliferative neoplasms. Structural modeling suggests a disrupted SH2B3 dimerization for this variant, which may have a potential functional impact. Although heterozygosity alone appears insufficient to drive disease, we suggest that SH2B3 p.Glu78Lys variant may determine a possible low-penetrance predisposition that warrants functional validation and broader screening.

Integrin-dependence of extramedullary erythropoiesis in the spleen of Jak2-V617F positive myeloproliferative neoplasm in mice

Conny K. Baldauf, Linda Poschmann, Bärbel Edelmann-Stephan,...Dimitrios Mougiakakos, Burkhart Schraven, Thomas Fischer

Open Access

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The molecular mechanisms driving splenomegaly in myeloproliferative neoplasms remain poorly understood. This study investigated the role of β1 and β2 integrins in regulation of spleen size. In Jak2-V617F knock-in mice, the response to neutralizing antibodies against β1/β2 integrins was evaluated by MRI, by analysis of spleen weight and by analysis of the cellular composition of spleens. Anti-integrin treatment significantly reduced the spleen volume by 30%. At the cellular level, anti-integrin treatment led to a substantial 30% decrease in erythroblast counts. Thus, our study identified a previously unrecognized role of the β1/β2-integrins in extramedullary erythropoiesis of the spleen in JAK2-V617F-induced disease.

Normal Hematopoiesis

Mouse Gata1 3′UTR modulates Gata1 levels to affect erythropoiesis

Ling Ling, Jiawen Huang, Zhichen Dai,...Jingyan Liang, Sheng He, Duonan Yu

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The role of the Gata1 3′UTR in mammals remains unclear. In this study, we generated Gata1 3′UTR knockout mice and observed a defect in erythropoiesis, evidenced by macrocytic anemia at baseline. Mechanistically, removing the Gata1 3′UTR destabilizes Gata1 mRNA and causes reduced expression of GATA1 protein. This low mRNA stability results from the dissociation of AU-rich elements in the 3′UTR from trans-acting factor ELAV-like family 1 (ELAVL1), rather than from loss of miRNA binding or loss of poly A sequences. Our results highlight the crucial role of the Gata1 3′UTR in erythroid development.

Endothelial protein C receptor CD201 is a better marker than stem cell antigen-1 to identify mouse long-term reconstituting hematopoietic stem cells following septic challenge

Kavita Bisht, Valérie Barbier, Svetlana Shatunova, Ingrid G. Winkler, Jean-Pierre Lévesque

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Stem cell antigen 1 (SCA1) has been used for decades to separate mouse hematopoietic stem and progenitor cell subsets; however, it fails to do so when mice are challenged by pathogens, interferons, or pathogen-associated molecular patterns because these stressors strongly upregulate SCA1 expression on myeloid and multipotent progenitors. Here, we showed that CD201 is a better marker of phenotypic and functional mouse hematopoietic stem cells because CD201 expression does not change and better identifies reconstituting stem cells upon inflammatory challenges, and CD201 is expressed on a wider range of mouse strains than SCA1.

Stem Cells

Pig and human adult hematopoietic stem and progenitor cells are overall transcriptionally similar

Emma Bailey, Foteini Kalampalika, Raúl Sánchez-Lanzas,...Amanda Jiménez-Pompa, Jun Wang, Miguel Ganuza

Open Access

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Allotransplantation provides a lifesaving treatment to hundreds of thousands of patients worldwide every year, including among others heart, kidney, liver and bone marrow (BM) transplants [1,2]. Yet, thousands of patients die yearly while waiting for a suitable donor and organ. Importantly, the number of patients in need of a transplant has disproportionally grown over the last 30 years compared with the number of performed transplants [1,2]. More than 100,000 patients in the United States were on a waiting list to receive a transplant in 2020 [1,2].

Malignant Hematopoiesis

ERK-mTOR crosstalk suppresses autophagy and upregulates proteasomal degradation pathway to confer chronic myeloid leukemia cells resistant to imatinib

Rajdeep Roy, Tamalika Paul, Pritam Kumar Das,...Siddhartha Sankar Ray, Maitreyee Bhattacharyya, Nabendu Biswas

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Maintaining proteome homeostasis is essential for cellular survival and function. Cells continuously synthesize and degrade proteins to ensure proper folding, assembly, and the timely removal of abnormal or misfolded proteins. Remarkably, nearly one-third of newly synthesized proteins are rapidly degraded, underscoring the critical role of protein turnover in cellular adaptation, especially under stress conditions [1].

Mixed-lineage leukemia cells undergo unique adaptations in the CNS niche

Alasdair Duguid, Camille Malouf, Leslie Nitsche, Christina Halsey, Katrin Ottersbach

Open Access

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Infant leukemia is an aggressive and biologically distinct malignancy, and is most frequently associated with rearrangements of the KMT2A gene (previously MLL). Although the majority of KMT2A-rearranged (KMT2A-r) infant leukemia cases present as pro-B cell acute lymphoblastic leukemia (B-ALL), a substantial minority exhibit acute myeloid or mixed-lineage phenotypes at diagnosis [1]. Lineage plasticity, particularly under therapeutic pressure, poses a significant clinical challenge where infants with KMT2A-r B-ALL treated with CD19-directed therapies such as chimeric antigen receptor (CAR) T cells or bispecific antibodies lose B-lineage identity, shifting toward a myeloid or mixed-lineage phenotype [2–4].