The March issue of Experimental Hematology is here!

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

Explore this Issue's Lineup:

Emerging paradigms in redox regulation: the role of selenoproteins in normal and malignant hematopoiesis

Yumi Aoyama, Hiromi Yamazaki, Daichi Inoue

Open Access

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Selenoproteins orchestrate hematopoietic fate through precise redox control, with selenocysteine residues enabling unique catalytic mechanisms. These antioxidant enzymes maintain redox homeostasis critical for HSC self-renewal and lineage commitment. Remarkably, selenoprotein deficiency triggers aberrant B-to-myeloid lineage conversion—revealing unexpected redox regulation of cell identity programs. Malignant cells exploit these same pathways for oxidative stress resistance and ferroptosis protection. This dichotomy between essential homeostatic functions and leukemic survival mechanisms presents opportunities for therapeutic intervention targeting specific nodes within selenoprotein networks.

Polycomb repressive complexes as therapeutic targets in hematologic malignancies

Makoto Yamagishi, Atsushi Iwama, Issay Kitabayashi

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Polycomb-group proteins form PRC1 and PRC2 complexes that mediate heritable transcriptional repression via H2AK119 ubiquitination and H3K27 trimethylation. Components of PRC1, including BMI1, BCOR, and PCGF1, and those of PRC2, such as EZH1/2, SUZ12, and EED, are essential for hematopoietic stem cell self-renewal and differentiation. Mutations in these complexes drive AML, MDS, and lymphomas. Elevated H3K27me3 is an early epigenetic hallmark of lymphoid malignancies. Because EZH2-selective inhibitors are limited by EZH1 redundancy, dual EZH1/2 inhibitors like valemetostat more effectively restore tumor-suppressor activity.

Tumor necrosis factor from leukemic environment stimulates hematopoietic stem/progenitor cells toward megakaryocyte/myeloid lineage bias

Hidekazu Nishikii, Riko Kikuchi, Takaharu Kimura,...Naoshi Obara, Satoshi Yamazaki, Shigeru Chiba

Open Access

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In a mouse model of MLL-AF9-induced acute myeloid leukemia, residual nonleukemic hematopoietic stem and progenitor cells (HSPCs) exhibited a megakaryocyte (MgK) and myeloid-biased transcriptional profile with activation of tumor necrosis factor (TNF) signaling and impaired repopulating activity. Ex vivo exposure of normal HSPCs to TNF-α reproduced these features, including MgK/myeloid lineage skewing and functional exhaustion. These findings indicate that TNF-α-driven inflammatory signaling contributes to the deterioration of normal hematopoiesis within leukemic bone marrow.

Splenic erythroblasts fuel leukemia progression through metabolic crosstalk

Jin Wang, Jian Xu

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A recent study by Li et al. [ 8 ] reveals a previously unrecognized erythroid cell population in the acute myeloid leukemia (AML) spleen that actively promotes leukemia growth through cytokine signaling and metabolic reprogramming

Loss of Ezh2 precipitates lethal disease progression in a mouse model of Calr-mutated myeloproliferative neoplasms

Koki Ueda, Yuka Sato, Keiji Minakawa, Saori Miura, Yuko Hashimoto, Kazuhiko Ikeda

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CALR-mutant myeloproliferative neoplasms occasionally progress to secondary myelofibrosis or acute myeloid leukemia, but the role of co-occurring EZH2 loss is unclear. Using a Calr-mutant knock-in mouse with inducible Ezh2 deletion, we show age-dependent evolution to either sMF-like or AML-like fatal disease. At a noncritical stage, peripheral counts remain near-normal whereas bone marrow hematopoietic stem and progenitor cell compartments are already distorted. AML-like, but not sMF-like, Flk2− CD48+ Lin− Sca-1+ c-Kit+ cells transmit leukemia and display enhanced fatty acid oxidation signatures, suggesting a distinct, potentially targetable metabolic bias.

Laminin receptor characterization in acute myeloid leukemia: integrin α7β1 defines leukemic cells with migratory potential

Elsa Görsch, Saskia Simone Rudat, Marlon Arnone,...Jan Weller, Gerd Klein, Claudia Lengerke

Open Access

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Acute myeloid leukemia (AML) cells engage with supportive bone marrow niche cells and extracellular matrix (ECM) proteins through surface receptors. Here, we demonstrated that high mRNA expression of the laminin receptors integrin α3β1, α6β1, α7β1, and BCAM correlates with poor overall survival. Moreover, ITGA7 expression marks leukemic cells displaying enhanced migratory potential. Together, we believe that our study significantly advances our understanding of AML-ECM interactions and provides important insights that might be instrumental in the development of future therapies addressing BM niche-mediated therapy resistance in AML.

Hematopoietic stem cell-independent and -dependent hematopoiesis: new insights and lineage-tracing methods

Miguel Ganuza, Momoko Yoshimoto

Open Access

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Recent advances in developmental biology have uncovered previously unrecognized hematopoietic waves, including hematopoietic stem cell (HSC)-independent progenitors that contribute to lifelong blood production. Using in vivo barcoding and lineage-tracing approaches, these studies redefine HSC numbers and behaviors, prompting new insights and ongoing debate in blood development.

Corrigendum to Analysis of risk factors for the early death of lymphocyte subsets in adult patients with secondary hemophagocytic lymphohistiocytosis Experimental Hematology Volume 153 (2025), 105286

Xiaosui Ling, Heng Chen, Xiuqin Zhang, Tangxing Xu, Aigen Deng, Jing Yang

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