U2AF1 mutation causes an oxidative stress and DNA repair defect in hematopoietic and leukemic cells.

U2AF1 is a core component of spliceosome and controls cell-fate specific alternative splicing. U2AF1 mutations have been frequently identified in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients, and mutations in U2AF1 are associated with poor prognosis in hematopoietic malignant diseases. Here, by forced expression of mutant U2AF1 (U2AF1 S34F) in hematopoietic and leukemic cell lines, we find that U2AF1 S34F causes increased reactive oxygen species (ROS) production.

Iron overload promotes the progression of MLL-AF9 induced acute myeloid leukemia by upregulation of FOS.

Systemic iron overload is a common clinical challenge leading to significantly serious complications in patients with acute myeloid leukemia (AML), which affects both the quality of life and the overall survival of patients. Symptoms can be relieved after iron chelation therapy in clinical practice. However, the roles and mechanisms of iron overload on the initiation and progression of leukemia remain elusive.

Sox13 and M2-like leukemia-associated macrophages contribute to endogenous IL-34 caused accelerated progression of acute myeloid leukemia.

Interleukin 34 (IL-34) mainly plays physiologic and pathologic roles through the sophisticated multi-ligand signaling system, macrophage colony-stimulating factor (M-CSF, CSF-1)/IL-34-CSF-1R axis, which exhibits functional redundancy, tissue-restriction and diversity. This axis is vital for the survival, differentiation and function of monocytic lineage cells and plays pathologic roles in a broad range of diseases. However, the role of IL-34 in leukemia has not been established.

Over expression of ubiquitin-conjugating enzyme E2O in bone marrow mesenchymal stromal cells partially attenuates acute myeloid leukaemia progression.

Bone marrow mesenchymal stromal cells (BM-MSCs) are implicated in the pathogenesis of acute myeloid leukaemia (AML). However, due to the high heterogeneity of AML the mechanism underlying the cross-talk between MSCs and leukaemia cells is not well understood. We found that mixed-lineage leukaemia-AF9 (MLL-AF9)-induced AML mice-derived MSCs had higher proliferative viability compared to wild-type mice-derived MSCs with ubiquitin-conjugating enzyme E2O (Ube2o) down-regulation.

Blockade of FGF2/FGFR2 partially overcomes bone marrow mesenchymal stromal cells mediated progression of T-cell acute lymphoblastic leukaemia.

The development of acute lymphoblastic leuakemia (ALL) is partly attributed to the effects of bone marrow (BM) microenvironment, especially mesenchymal stromal cells (MSCs), which interact bilaterally with leukaemia cells, leading to ALL progression. In order to find MSCs-based microenvironment targeted therapeutic strategies, Notch1-induced T-cell ALL (T-ALL) mice models were used and dynamic alterations of BM-MSCs with increased cell viability during T-ALL development was observed. In T-ALL mice derived stroma-based condition, leukaemia cells showed significantly elevated growth capacity indicating that MSCs participated in leukaemic niche formation.

Fbxw11 impairs the repopulation capacity of hematopoietic stem/progenitor cells.

Background: The ubiquitin-proteasome system plays important roles in maintaining the self-renewal and differentiation of stem and progenitor cells through highly ordered degradation of cellular proteins. Fbxw11, an E3 ligase, participates in many important biological processes by targeting a broad range of proteins. However, its roles in hematopoietic stem/progenitor cells (HSPCs) have not been established.

DDIT4 mediates the proliferation-promotive effect of IL-34 in human monocytic leukemia cells.

IL-34 is involved in a broad range of cancer. that IL-34 promoted the proliferation and colony formation of human acute monocytic leukemia (AMoL) cells. However, the mechanism has not been elucidated.

Loss of IRF7 accelerates acute myeloid leukemia progression and induces VCAM1-VLA-4 mediated intracerebral invasion.

Interferon regulatory factor 7 (IRF7) is widely studied in inflammatory models. Its effects on malignant progression have been documented mainly from the perspective of the microenvironment. However, its role in leukemia has not been established.

MiR-451a enhances the phagocytosis and affects both M1 and M2 polarization in macrophages.

Leukemia associated macrophages (LAMs), which are different from tumor-associated macrophages as well as classical M1 and M2 macrophages, are specifically activated by leukemic microenvironment. We have reported the heterogeneity of gene expression profiles in LAMs. However, the expression profiles of microRNA (miRNA) in LAMs and their regulatory mechanisms have not been established.

Peritoneal resident macrophages in mice with MLL-AF9-induced acute myeloid leukemia show an M2-like phenotype.

Background: Acute myeloid leukemia (AML) is a devastating disease with a poor prognosis. Innate and adaptive immunity is closely related to the progression of leukemia. Macrophages within the leukemic microenvironment have a tendency toward a leukemia-permissive phenotype.

Single-cell transcriptomic landscape of human blood cells.

High throughput single-cell RNA-seq has been successfully implemented to dissect the cellular and molecular features underlying hematopoiesis. However, an elaborate and comprehensive transcriptome reference of the whole blood system is lacking. Here, we profiled the transcriptomes of 7551 human blood cells representing 32 immunophenotypic cell types, including hematopoietic stem cells, progenitors and mature blood cells derived from 21 healthy donors.

Monocyte-Derived Leukemia-Associated Macrophages Facilitate Extramedullary Distribution of T-cell Acute Lymphoblastic Leukemia Cells.

Macrophages play important roles in both physiologic and pathologic processes and arise from successive waves of embryonic and adult hematopoiesis. Monocyte-derived macrophages (MOMF) exert distinct functions under pathologic conditions, and leukemia-associated macrophages (LAM) show considerable diversities in activation and functional phenotype. However, their origin and pathologic roles have not been well elucidated.

two-photon microscopy reveals the contribution of Sox9 cell to kidney regeneration in a mouse model with extracellular vesicle treatment.

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been shown to stimulate regeneration in the treatment of kidney injury. Renal regeneration is also thought to be stimulated by the activation of Sox9 cells. However, whether and how the activation mechanisms underlying EV treatment and Sox9 cell-dependent regeneration intersect is unclear.

P2X7 promotes the progression of MLL-AF9 induced acute myeloid leukemia by upregulation of Pbx3.

Nucleotides mediate intercellular communication by activating purinergic receptors and take part in various physiological and pathological processes. Abnormal purinergic signaling plays important roles in malignant progression. P2X7, which belongs to the P2X family of purinergic receptors, is abnormally expressed in various types of malignancies including leukemia.

Blocking migration of regulatory T cells to leukemic hematopoietic microenvironment delays disease progression in mouse leukemia model.

Blocking the migration of regulatory T cells (Tregs) to the tumor microenvironment is a promising strategy for tumor immunotherapy. Treg accumulation in the leukemic hematopoietic microenvironment (LHME) has adverse impacts on patient outcomes. The mechanism and effective methods of disrupting Treg accumulation in the LHME have not been well established.

Macrophages in leukemia microenvironment.

Macrophages, the important component of tissue microenvironment, play important roles in both physiological and pathological processes, including tumor and leukemia. Tumor-associated macrophages are involved in tumor proliferation, angiogenesis, invasion, metastasis, and chemotherapy resistance. In leukemia, macrophages are educated by leukemia microenvironment to obtain specific activated phenotype and participate in leukemia progression.

Repolarizing heterogeneous leukemia-associated macrophages with more M1 characteristics eliminates their pro-leukemic effects.

Macrophages exhibit phenotypic heterogeneity under both physiological and pathological conditions. Applications targeting M2-like tumor-associated macrophages (TAMs) improve outcome in solid tumors. Considerable differences are detected between leukemia-associated macrophages (LAMs) and TAMs.

Fbxw11 promotes the proliferation of lymphocytic leukemia cells through the concomitant activation of NF-κB and β-catenin/TCF signaling pathways.

The ubiquitin-proteasome system (UPS) participates in both physiological and pathological processes through the posttranslational regulation of intracellular signal transduction pathways. F-box and WD-40 domain protein 11 (Fbxw11) is a component of the SCF (Skp1-Cul1-F-box) E3 ubiquitin ligase complex. Fbxw11 regulates various signal transduction pathways, and it may have pathological roles in tumorigenesis.

Heterogeneous effects of M-CSF isoforms on the progression of MLL-AF9 leukemia.

Macrophage colony-stimulating factor (M-CSF) regulates both malignant cells and microenvironmental cells. Its splicing isoforms show functional heterogeneity. However, their roles on leukemia have not been well established.

Characteristics of NK cells from leukemic microenvironment in MLL-AF9 induced acute myeloid leukemia.

NK cells are indispensable components of tissue microenvironment and play vital in both innate and adaptive immunity. The activation and function of NK cells are affected by tumor microenvironments. NK cells are also important players in leukemic microenvironment.

Hepatic leukemia-associated macrophages exhibit a pro-inflammatory phenotype in Notch1-induced acute T cell leukemia.

Tumor-associated macrophages (TAMs) are well accepted and the pathological role of macrophages in hematopoietic malignancies have been proposed. Hepatomegaly is frequently observed in T cell acute lymphoblastic leukemia (T-ALL) patients with poor prognosis. However, the role of leukemia-associated macrophages (LAMs) in hepatic microenvironment remains unclear.

Characterization of peritoneal leukemia-associated macrophages in Notch1-induced mouse T cell acute lymphoblastic leukemia.

Macrophages, which have remarkable plasticity, are indispensable cellular components and play essential roles in both innate and adaptive immune responses. Peritoneal macrophages show unique gene expression profile and peritoneal cavity is also involved in leukemia. However, the characteristics of peritoneal leukemia-associated macrophages (Per LAMs) have not been established.