The January issue of Experimental Hematology is here!

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

Explore this Issue's Lineup:

Developmental hematopoiesis: innate programming of αβ T cells

Isabel M. Forlastro, Norah L. Smith, Emily N. Kulp, Momoko Yoshimoto, Brian D. Rudd

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The hematopoietic system produces blood and immune cells in waves tailored to the unique needs of the developing organism. Such waves are well characterized for many innate immune populations (e.g., microglia and Kupffer cells) and B cell subsets (e.g., B1a, B1b, and B2 cells), which arise at different stages of development [1–3]. In contrast, the role of developmental origin in αβ T cells is less defined. This knowledge gap persists even as we recognize that the thymus generates γδ T cells in discrete waves, each containing functionally distinct subsets with unique T-cell receptors (TCRs; Vγ3, Vγ4, and Vγ5), effector functions, and tissue residencies [4–6].

Feedback loops in B-cell chromatin regulation as a therapeutic target for modulating antibody production and malignancies: insights from BACH2

Kyoko Ochiai, Kazuhiko Igarashi

Open Access

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B cells play a central role in the production of antigen-specific antibodies during acquired immunity. They are derived from hematopoietic stem cells and undergo early developmental stages in the bone marrow. Following the expression of surface immunoglobulin (Ig)M, the B-cell receptor (BCR), naïve B cells circulate through the bloodstream, localizing to the secondary lymphoid organs, such as the spleen and lymph nodes, while maintaining a quiescent cell status. After encountering a cognitive antigen, naïve B cells undergo clonal expansion and differentiate into antibody-secreting plasma cells.

Optimal ex vivo production of functional neutrophils is dependent on the source of CD34+ human hematopoietic progenitors

Kyle D. Timmer, Daniel J. Floyd, Nathan E. Jeffries, ... Vincent B. Ho, David B. Sykes, Michael K. Mansour

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Sources of CD34+ hematopoietic stem and progenitor cells (HSPC) were investigated for their capacity to proliferate and differentiate human neutrophils ex vivo. Among Umbilical Cord (UCB) and bone marrow-derived HSPCs, UCB was most proliferative during a six-day expansion phase. All three cell sources produced functional neutrophils capable of phagocytosing live Candida albicans and producing reactive oxygen species. Single-cell RNA sequencing demonstrated our ex vivo-generated cells were transcriptionally consistent with known patterns of myeloid differentiation. These data identify optimal conditions for the expansion of human neutrophil progenitors.

Analysis of risk factors for early death of lymphocyte subsets in adult patients with secondary hemophagocytic lymphohistiocytosis

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

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Hemophagocytic lymphohistiocytosis (HLH), also known as a hemophagocytic syndrome (HPS), is an excess inflammatory response syndrome caused by genetic or acquired immune dysregulation [1,2]. Depending on the different causes, the disease can be classified into two categories: familial hemophagocytic lymphohistiocytosis (fHLH) and secondary hemophagocytic lymphohistiocytosis (sHLH) [3]. fHLH is mainly seen in newborns and is a genetic disease. Patients often have defects in HLH-related genes, and diagnosis relies on gene detection [4].

Upfront menin-inhibitor resistance in multiply pretreated leukemias

Leila Mahdavi, Fatemeh Alikarami, Haley Goodrow,...Junwei Shi, Hongbo M. Xie, Kathrin M. Bernt

Open Access

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Inhibitors of the menin-KMT2A interaction are promising agents for the treatment of KMT2A-rearranged leukemias. We evaluated menin inhibition in patient-derived xenografts of KMT2A-rearranged leukemias with high-risk features. Three acute myeloid leukemias with high-risk fusion partners (mixed-lineage leukemia-10 [MLLT10] and mixed-lineage leukemia-4 [MLLT4]) and two infant acute lymphocytic leukemia (ALL) samples were sensitive to menin inhibition. We also evaluated serial samples from two patients with multiply relapsed ALL.

Cohesin haploinsufficiency is tolerated in Cbfb::MYH11-driven murine acute myeloid leukemia

Shannon E. Conneely, Alexis Quezada, Kristen J. Kurtz,...Paul P. Liu, Debananda Pati, Rachel E. Rau

Open Access

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Cohesin gene mutations occur in most subtypes of acute myeloid leukemia but are absent from CBFB::MYH11 AML. To investigate whether cohesin genes serve as a therapeutic target in CBFB::MYH11 AML, we used murine models of cohesin mutations combined with an inducible Cbfb::MYH11. We demonstrate that intact cohesin function is dispensable for Cbfb::MYH11-driven leukemia. However, Rad21 and Smc3 deletion demonstrated differential effects on leukemia development and secondary engraftment, challenging current assumptions about cohesin biology.

Cytoreductive treatment differentially affects platelet size and cytoskeletal megakaryocyte organization during thrombopoiesis in myeloproliferative neoplasms

Adela S. Cellucci, Danila B. Yañuk, Paola R. Lev,...Laureano J. Kamiya, Paula G. Heller, Rosana F. Marta

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Platelet size is increased in myeloproliferative patients treated with anagrelide, α-interferon, and ruxolitinib and decreased in those under hydroxyurea. Only anagrelide and α-interferon alter proplatelet architecture and induce microtubular disorganization in normal megakaryocyte culture. Additionally, anagrelide alters actin cytoskeleton and decreases megakaryocyte RANTES expression and release. These abnormalities are reverted by RANTES addition. RANTES plasmatic levels and platelet RNA expression are decreased in anagrelide-treated versus untreated patients, suggesting in vitro findings reflect anagrelide action in vivo.