Self-renewal and multidirectional differentiation of hematopoietic stem cells (HSCs) are strictly regulated by numerous cellular components and cytokines in the bone marrow (BM) microenvironment. Several cell types that regulate HSC niche have been identified, including both non-hematopoietic cells and HSC-derived cells. Specific changes in the niche composition can result in hematological malignancies. Furthermore, processes such as homing, proliferation, and differentiation of HSCs are strongly controlled by the BM niche and have been reported to be related to the success of hematopoietic stem cell transplantation (HSCT). Single-cell sequencing and in vivo imaging are powerful techniques to study BM microenvironment in hematological malignancies and after HSCT. In this review, we discuss how different components of the BM niche, particularly non-hematopoietic and hematopoietic cells, regulate normal hematopoiesis, and changes in the BM niche in leukemia and after HSCT. We believe that this comprehensive review will provide clues for further research on improving HSCT efficiency and exploring potential therapeutic targets for leukemia.

Poor graft function (PGF) is a life-threatening complication that occurs after transplantation and has a poor prognosis. With the rapid development of haploidentical hematopoietic stem cell transplantation, the pathogenesis of PGF has become an important issue. Studies of the pathogenesis of PGF have resulted in some success in CD34⁺-selected stem cell boosting. Mesenchymal stem cells, N-acetyl-l-cysteine, and eltrombopag have also been investigated as therapeutic strategies for PGF. However, predicting and preventing PGF remains challenging. Here, we propose that the seed, soil, and insect theories of aplastic anemia also apply to PGF; CD34⁺ cells are compared to seeds; the bone marrow microenvironment to soil; and virus infection, iron overload, and donor-specific anti-human leukocyte antigen antibodies to insects. From this perspective, we summarize the available information on the common risk factors of PGF, focusing on its potential mechanism. In addition, the safety and efficacy of new strategies for treating PGF are discussed to provide a foundation for preventing and treating this complex clinical problem.

The constitutive hyper-activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways has frequently been associated with acute myeloid leukemia (AML). While many inhibitors targeting these pathways have been developed, the anti-leukemic effect was not as robust as expected. As part of the molecular link between PI3K/Akt and mTOR kinase, the role of Rheb1 in AML remains unexplored. Our study aims to explore the role of Rheb1 in AML and estimate whether Rheb1 could be a potential target of AML treatment. The expressions of Rheb1 and other indicated genes were analyzed using real-time PCR. AML mouse model was established by retrovirus transduction. Leukemia cell properties and related signaling pathways were dissected by in vitro and in vivo studies. The transcriptional changes were analyzed via gene chip analysis. Molecular reagents including mTOR inhibitor and mTOR activator were used to evaluate the function of related signaling pathway in the mouse model. We observed that Rheb1 is overexpressed in AML patients and the change of Rheb1 level in AML patients is associated with their median survival. Using a Rheb1-deficient MLL-AF9 murine AML model, we revealed that Rheb1 deletion prolonged the survival of AML mice by weakening LSC function. In addition, Rheb1 deletion arrested cell cycle progression and enhanced apoptosis of AML cells. Furthermore, while Rheb1 deletion reduced mTORC1 activity in AML cells, additional rapamycin treatment further decreased mTORC1 activity and increased the apoptosis of Rheb1 Δ/Δ AML cells. The mTOR activator 3BDO partially rescued mTORC1 signaling and inhibited apoptosis in Rheb1 Δ/Δ AML cells. Our data suggest that Rheb1 promotes AML progression through mTORC1 signaling pathway and combinational drug treatments targeting Rheb1 and mTOR might have a better therapeutic effect on leukemia.

Small extracellular vesicles (sEV) transfer cargos between cells and participate in various physiological and pathological processes through their autocrine and paracrine effects. However, the pathological mechanisms employed by sEV-encapsulated microRNA (miRNA) in acute myeloid leukemia (AML) are still obscure. In this study, we aimed to investigate the effects of AML cell-derived sEV (AML-sEV) on AML cells and delineate the underlying mechanisms. We initially used high-throughput sequencing to identify miR-221-3p as the miRNA prominently enriched in AML-sEV. Our findings revealed that miR-221-3p promoted AML cell proliferation and leukemogenesis by accelerating cell cycle entry and inhibiting apoptosis. Furthermore, Gbp2 was confirmed as a target gene of miR-221-3p by dual luciferase reporter assays and rescue experiments. Additionally, AML-sEV impaired the clonogenicity, particularly the erythroid differentiation ability, of hematopoietic stem and progenitor cells. Taken together, our findings reveal how sEV-delivered miRNA contribute to AML pathogenesis, which can be exploited as a potential therapeutic target to attenuate AML progression.

Lymphoma is a highly heterogeneous hematologic malignancy characterized by intricate molecular and pathological mechanisms. Key mechanisms contributing to its complexity include malignant clonal evolution driven by somatic mutations, epigenetic modifications affecting gene regulation and cellular behavior, and dynamic tumor microenvironment remodeling. These factors collectively undermine the efficacy of conventional therapeutic strategies. Differences in the molecular mechanisms of different subtypes lead to heterogeneity in treatment response and recurrence of drug resistance. Current and future investigative priorities emphasize molecular stratification, precision diagnosis and therapeutic strategies, advancement of novel diagnostic tools, and the implementation of artificial intelligence (AI) for integrative analysis of high-dimensional biological data. Moreover, emerging areas such as microbiome-targeted interventions are being explored to improve clinical outcomes and support the evolution of precision oncology in lymphoma treatment.

Genetic mutations in the β-globin gene lead to a decrease or removal of the β-globin chain, causing the build-up of unstable alpha-hemoglobin. This condition is referred to as beta-thalassemia (BT). The present treatment strategies primarily target the correction of defective erythropoiesis, with a particular emphasis on gene therapy and hematopoietic stem cell transplantation. However, the presence of inefficient erythropoiesis in BT bone marrow (BM) is likely to disturb the previously functioning BM microenvironment. This includes accumulation of various macromolecules, damage to hematopoietic function, destruction of bone cell production and damage to osteoblast(OBs), and so on. In addition, the changes of BT BM microenvironment may have a certain correlation with the occurrence of hematological malignancies. Correction of the microenvironment can be achieved through treatments such as iron chelation, antioxidants, hypoglycemia, and biologics. Hence, This review describes damage in the BT BM microenvironment and some potential remedies.