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Factors associated with chronic elevation of the blood lactate levels in patients undergoing chronic maintenance hemodialysis (hereinafter, hemodialysis patients) have not yet been thoroughly investigated. The purpose of the present study was to clarify factors associated with elevated blood lactate levels in hemodialysis patients. We divided the hemodialysis patients into two groups according the blood lactate levels (the high blood lactate group [> 2 mmol/L] and normal blood lactate group), and conducted a retrospective comparison of the following items between the two groups: (1) the creatinine generation rate (%CGR) and the geriatric nutrition risk index (GNRI) as indices of the nutritional status; (2) the left ventricular ejection fraction (LVEF) and E/A, an indicator of diastolic function; (3) the ankle-brachial index (ABI) and transcutaneous partial pressure of oxygen as indices of the adequacy of circulation in the peripheral blood vessels of the lower extremities; (4) the white blood cell count and serum level of C-reactive protein (CRP) before dialysis as markers of an inflammatory state. The mean age and serum CRP level were significantly higher in the high blood lactate group than in the normal blood lactate group. There were no significant differences in the markers of the nutritional status, cardiac function, or adequacy of circulation in the peripheral blood vessels of the lower extremities between the two groups. Advanced age and a state of chronic inflammation appear to be associated with elevated blood lactate levels in patients undergoing chronic maintenance hemodialysis.
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Fallo Renal Crónico , Humanos , Anciano , Volumen Sistólico , Estudios Retrospectivos , Función Ventricular Izquierda , Diálisis Renal , Estado Nutricional , Factores de RiesgoRESUMEN
We report on the high potential of a honeycomb reactor for the use in aerobic oxidation under continuous-flow conditions. The honeycomb reactor is made of porous material with narrow channels separated by porous walls allowing for high density accumulation in the reactor. This structure raised the mixing efficiency of a gas-liquid reaction system, and it effectively accelerated the aerobic oxidation of benzyl alcohols to benzaldehydes under continuous-flow conditions. This reactor is a promising device for streamlining aerobic oxidation with high process safety because it is a closed system.
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Acute respiratory distress syndrome (ARDS) is a critical illness syndrome characterized by dysregulated pulmonary inflammation. Currently, effective pharmacological treatments for ARDS are unavailable. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor type 1a (GHS-R1a), has a pivotal role in regulating energy metabolism and immunomodulation. The role of endogenous ghrelin in ARDS remains unresolved. Herein, we investigated the role of endogenous ghrelin signaling by using GHS-R1a-null (ghsr-/-) mice and lipopolysaccharide (LPS)-induced ARDS model. Ghsr-/- mice survived longer than controls after LPS-induced lung injury. Ghsr-/- mice showed lower levels of pro-inflammatory cytokines and higher oxygenation levels after lung injury. The peritoneal macrophages isolated from ghsr-/- mice exhibited lower levels of cytokines production and oxygen consumption rate after LPS stimulation. Our results indicated that endogenous ghrelin plays a pivotal role in initiation and continuation in acute inflammatory response in LPS-induced ARDS model by modulating macrophage activity, and highlighted endogenous GHS-R1a signaling in macrophage as a potential therapeutic target in this relentless disease.
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Regulación hacia Abajo , Lesión Pulmonar/patología , Macrófagos Peritoneales/patología , Receptores de Ghrelina/deficiencia , Animales , Respiración de la Célula , Citocinas/genética , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Lipopolisacáridos , Lesión Pulmonar/complicaciones , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , FN-kappa B/metabolismo , Neumonía/complicaciones , Neumonía/patología , Alveolos Pulmonares/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Ghrelina/metabolismoRESUMEN
Synthetic polymer nanoparticles (NPs) that recognize and neutralize target biomacromolecules are of considerable interest as "plastic antibodies", synthetic mimics of antibodies. However, monomer sequences in the synthetic NPs are heterogeneous. The heterogeneity limits the target specificity and safety of the NPs. Herein, we report the synthesis of NPs with uniform monomer sequences for recognition and neutralization of target peptides. A multifunctional oligomer with a precise monomer sequence that recognizes the target peptide was prepared via cycles of reversible addition-fragmentation chain transfer (RAFT) polymerization and flash chromatography. The oligomer or blend of oligomers was used as a chain transfer agent and introduced into poly(N-isopropyl acrylamide) hydrogel NPs by radical polymerization. Evaluation of the interaction with the peptides revealed that multiple oligomers in NPs cooperatively recognized the sequence of the target peptide and neutralized its toxicity. Effect of sequence, combination, density and molecular weight distribution of precision oligomers on the affinity to the peptides was also investigated.
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Nanopartículas , Polímeros , Hidrogeles , Nanopartículas/química , Péptidos/química , Polimerizacion , Polímeros/químicaRESUMEN
Diverse metabolic changes are induced by various driver oncogenes during the onset and progression of leukemia. By upregulating glycolysis, cancer cells acquire a proliferative advantage over normal hematopoietic cells; in addition, these changes in energy metabolism contribute to anticancer drug resistance. Because leukemia cells proliferate by consuming glucose as an energy source, an alternative nutrient source is essential when glucose levels in bone marrow are insufficient. We profiled sugar metabolism in leukemia cells and found that mannose is an energy source for glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway. Leukemia cells express high levels of phosphomannose isomerase (PMI), which mobilizes mannose to glycolysis; consequently, even mannose in the blood can be used as an energy source for glycolysis. Conversely, suppression of PMI expression or a mannose load exceeding the processing capacity of PMI inhibited transcription of genes related to mitochondrial metabolism and the TCA cycle, therefore suppressing the growth of leukemia cells. High PMI expression was also a poor prognostic factor for acute myeloid leukemia. Our findings reveal a new mechanism for glucose starvation resistance in leukemia. Furthermore, the combination of PMI suppression and mannose loading has potential as a novel treatment for driver oncogene-independent leukemia.
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Leucemia/tratamiento farmacológico , Manosa-6-Fosfato Isomerasa/metabolismo , Manosa/administración & dosificación , Regulación hacia Arriba , Animales , Línea Celular Tumoral , Ciclo del Ácido Cítrico/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glucólisis/efectos de los fármacos , Humanos , Células K562 , Leucemia/enzimología , Leucemia/genética , Leucemia/patología , Manosa/farmacología , Manosa-6-Fosfato Isomerasa/antagonistas & inhibidores , Ratones , Vía de Pentosa Fosfato/efectos de los fármacos , Pronóstico , Células THP-1 , Regulación hacia Arriba/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Oncogenic mutations confer on cells the ability to propagate indefinitely, but whether oncogenes alter the cell fate of these cells is unknown. Here, we show that the transcriptional regulator PRDM16s causes oncogenic fate conversion by transforming cells fated to form platelets and erythrocytes into myeloid leukemia stem cells (LSCs). Prdm16s expression in megakaryocyte-erythroid progenitors (MEPs), which normally lack the potential to generate granulomonocytic cells, caused AML by converting MEPs into LSCs. Prdm16s blocked megakaryocytic/erythroid potential by interacting with super enhancers and activating myeloid master regulators, including PU.1. A CRISPR dropout screen confirmed that PU.1 is required for Prdm16s-induced leukemia. Ablating PU.1 attenuated leukemogenesis and reinstated the megakaryocytic/erythroid potential of leukemic MEPs in mouse models and human AML with PRDM16 rearrangement. Thus, oncogenic PRDM16 s expression gives MEPs an LSC fate by activating myeloid gene regulatory networks.
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Transformación Celular Neoplásica/patología , Proteínas de Unión al ADN/genética , Leucemia Mieloide Aguda/patología , Células Progenitoras de Megacariocitos y Eritrocitos/patología , Factores de Transcripción/genética , Animales , Transformación Celular Neoplásica/genética , Regulación Leucémica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Leucemia Mieloide Aguda/genética , Células Progenitoras de Megacariocitos y Eritrocitos/metabolismo , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas/genética , Transactivadores/genética , Translocación GenéticaRESUMEN
BACKGROUND: Endoscopic submucosal dissection (ESD) is currently a common procedure although it requires a long procedural time. We conducted a prospective study to determine the efficacy and safety of lidocaine injection for shortening the procedural time and relieving bowel peristalsis during ESD. METHODS: A multicenter randomized controlled study was conducted in three hospitals. Ninety-one patients who underwent colorectal ESD were enrolled. Patients were randomly divided into two groups using the envelope method: the lidocaine group and saline group. The primary endpoint was the procedural time, and the secondary endpoints were the procedural time in each part of the colon and the grade of bowel peristalsis and the incidence and amounts of antispasmodic drugs use and adverse events. RESULTS: The patients' demographics were not markedly different between the two groups. The mean procedural time in the lidocaine group was not markedly different from that in the saline group. In contrast, at the proximal site, the procedural time in the lidocaine group (57 min) was significantly shorter in the saline group (80 min). The grade of bowel peristalsis in the lidocaine group (0.67) was significantly lower than in the saline group (1.17). Antispasmodic drug use was significantly rarer in the lidocaine group than in the saline group. The incidence of adverse events was not markedly different between the two groups. CONCLUSIONS: Local lidocaine injection is a feasible option for preventing bowel peristalsis, particularly in the proximal colon, leading to a reduced procedural time for ESD and decreased antispasmodic drug use. University Hospital Medical Information Network Center (UMIN number: 000022843).
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Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Lidocaína/uso terapéutico , Neoplasias Colorrectales/cirugía , Disección , Humanos , Lidocaína/administración & dosificación , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Metabolic reprogramming of leukemia cells is important for survival, proliferation, and drug resistance under conditions of metabolic stress in the bone marrow. Deregulation of cellular metabolism, leading to development of leukemia, occurs through abnormally high expression of transcription factors such as MYC and Ecotropic Virus Integration site 1 protein homolog (EVI1). Overexpression of EVI1 in adults and children with mixed lineage leukemia-rearrangement acute myeloid leukemia (MLL-r AML) has a very poor prognosis. To identify a metabolic inhibitor for EVI1-induced metabolic reprogramming in MLL-r AML, we used an XFp extracellular flux analyzer to examine metabolic changes during leukemia development in mouse models of AML expressing MLL-AF9 and Evi1 (Evi1/MF9). Oxidative phosphorylation (OXPHOS) in Evi1/MF9 AML cells accelerated prior to activation of glycolysis, with a higher dependency on glutamine as an energy source. Furthermore, EVI1 played a role in glycolysis as well as driving production of metabolites in the tricarboxylic acid cycle. L-asparaginase (L-asp) exacerbated growth inhibition induced by glutamine starvation and suppressed OXPHOS and proliferation of Evi1/MF9 both in vitro and in vivo; high sensitivity to L-asp was caused by low expression of asparagine synthetase (ASNS) and L-asp-induced suppression of glutamine metabolism. In addition, samples from patients with EVI1+MF9 showed low ASNS expression, suggesting that it is a sensitive marker of L-asp treatment. Clarification of metabolic reprogramming in EVI1+ leukemia cells may aid development of treatments for EVI1+MF9 refractory leukemia.
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Leucemia Mieloide Aguda , Proto-Oncogenes , Adulto , Asparaginasa , Proteínas de Unión al ADN/genética , Humanos , Leucemia Mieloide Aguda/genética , Proteína del Locus del Complejo MDS1 y EV11/genética , Proto-Oncogenes/genética , Factores de Transcripción/genéticaRESUMEN
A 49-year-old man underwent low anterior resection for rectal cancer with liver and lung metastases. He refused additional systemic chemotherapy. After 10 months, he presented with a painful anal tumor and we performed trans-anal resection of the tumor. Histopathological examination revealed a metastasis of the rectal cancer. Chemotherapy was performed subsequently. He survived 7 months after the second surgery without local recurrence. We reported a rare case of anal metastasis from rectal cancer.
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Neoplasias del Ano , Neoplasias Pulmonares , Neoplasias del Recto , Neoplasias del Ano/tratamiento farmacológico , Neoplasias del Ano/cirugía , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/cirugíaRESUMEN
Systemic mastocytosis (SM) is a disorder characterized by abnormal proliferation of mast cells with KIT mutations, especially in codon 816. The prognosis of patients developing acute myeloid leukemia (AML) from SM is extremely poor, and hematopoietic cell transplantation is recommended. Herein, we describe a case of an 8-year-old female diagnosed with SM developing AML. A KIT M541L variant in SM was identified in leukemic cells, normal hematopoietic cells, and buccal mucosal cells, suggesting a germline polymorphism. The patient has remained in complete remission for 39 months after completion of chemotherapy. SM developing AML without a KIT D816 mutation may be not necessarily associated with a poor prognosis.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Mastocitosis Sistémica/complicaciones , Niño , Femenino , Humanos , Leucemia Mieloide Aguda/etiología , Leucemia Mieloide Aguda/patología , Pronóstico , Inducción de RemisiónRESUMEN
Here, we report the case of a 9-year-old girl with acute myeloid leukemia (AML) developed from systemic mastocytosis (SM). She experienced bladder and rectal disturbance due to an extramedullary nodule in the paraspinal region of the sacrum. Cytogenetic and genetic analyses of leukemic cells revealed the KIT D816Y mutation besides t (8;21) (q22:q22) /RUNX1-RUNX1T1. Despite receiving proton beam therapy after conventional chemotherapy, the patient relapsed after 2 months. As SM-AML with the KIT D816 mutation in adults exhibits a poor prognosis, hematopoietic stem cell transplantation is recommended. Owing to a few reports of SM-AML in children, the standard therapy for pediatric cases has not been established to date. Based on our experience and the related literature, the prognosis of childhood SM-AML could be as poor as in adults. Hence, further investigation, including mutational analyses of the KIT gene, is warranted to establish a risk-oriented strategy for managing childhood SM-AML.
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Leucemia Mieloide Aguda/complicaciones , Mastocitosis Sistémica/complicaciones , Niño , Femenino , Humanos , Mastocitosis Sistémica/tratamiento farmacológico , Mutación , Pronóstico , Recurrencia , Translocación GenéticaRESUMEN
The presence of a BCR-ABL1 fusion gene is necessary for the pathogenesis of chronic myeloid leukemia (CML) through t(9;22)(q34;q11) translocation. Imatinib, an ABL tyrosine kinase inhibitor, is dramatically effective in CML patients; however, 30% of CML patients will need further treatment due to progression of CML to blast crisis (BC). Aberrant high expression of ecotropic viral integration site 1 (EVI1) is frequently observed in CML during myeloid-BC as a potent driver with a CML stem cell signature; however, the precise molecular mechanism of EVI1 transcriptional regulation during CML progression is poorly defined. Here, we demonstrate the transcriptional activity of EVI1 is dependent on activation of lymphoid enhancer-binding factor 1 (LEF1)/ß-catenin complex by BCR-ABL with loss of p53 function during CML-BC. The activation of ß-catenin is partly dependent on BCR-ABL expression through enhanced GSK3ß phosphorylation, and EVI1 expression is directly enhanced by the LEF1/ß-catenin complex bound to the EVI1 promoter region. Moreover, the loss of p53 expression is inversely correlated with high expression of EVI1 in CML leukemia cells with an aggressive phase of CML, and a portion of the activation mechanism of EVI1 expression is dependent on ß-catenin activation through GSK3ß phosphorylation by loss of p53. Therefore, we found that the EVI1 activation in CML-BC is dependent on LEF1/ß-catenin activation by BCR-ABL expression with loss of p53 function, representing a novel selective therapeutic approach targeting myeloid blast crisis progression.
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Crisis Blástica/genética , Proteínas de Unión al ADN/genética , Regulación Leucémica de la Expresión Génica , Factor de Unión 1 al Potenciador Linfoide/metabolismo , Proto-Oncogenes/genética , Factores de Transcripción/genética , Proteína p53 Supresora de Tumor/metabolismo , beta Catenina/metabolismo , Animales , Crisis Blástica/metabolismo , Crisis Blástica/patología , Línea Celular Tumoral , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Proteína del Locus del Complejo MDS1 y EV11 , Ratones , Activación TranscripcionalRESUMEN
Thymine DNA glycosylase (TDG) is a member of the uracil DNA glycosylase (UDG) superfamily of DNA repair enzymes. Owing to its ability to excise thymine when mispaired with guanine, it was proposed to act against the mutability of 5-methylcytosine (5-mC) deamination in mammalian DNA. However, TDG was also found to interact with transcription factors, histone acetyltransferases and de novo DNA methyltransferases, and it has been associated with DNA demethylation in gene promoters following activation of transcription, altogether implicating an engagement in gene regulation rather than DNA repair. Here we use a mouse genetic approach to determine the biological function of this multifaceted DNA repair enzyme. We find that, unlike other DNA glycosylases, TDG is essential for embryonic development, and that this phenotype is associated with epigenetic aberrations affecting the expression of developmental genes. Fibroblasts derived from Tdg null embryos (mouse embryonic fibroblasts, MEFs) show impaired gene regulation, coincident with imbalanced histone modification and CpG methylation at promoters of affected genes. TDG associates with the promoters of such genes both in fibroblasts and in embryonic stem cells (ESCs), but epigenetic aberrations only appear upon cell lineage commitment. We show that TDG contributes to the maintenance of active and bivalent chromatin throughout cell differentiation, facilitating a proper assembly of chromatin-modifying complexes and initiating base excision repair to counter aberrant de novo methylation. We thus conclude that TDG-dependent DNA repair has evolved to provide epigenetic stability in lineage committed cells.
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Embrión de Mamíferos/embriología , Embrión de Mamíferos/metabolismo , Desarrollo Embrionario/genética , Epigénesis Genética/genética , Genes Letales/genética , Fenotipo , Timina ADN Glicosilasa/metabolismo , Animales , Diferenciación Celular/genética , Linaje de la Célula/genética , Cromatina/genética , Cromatina/metabolismo , Islas de CpG/genética , Metilación de ADN , Reparación del ADN , Embrión de Mamíferos/enzimología , Fibroblastos/metabolismo , Eliminación de Gen , Regulación del Desarrollo de la Expresión Génica , Genes Esenciales/genética , Histonas/metabolismo , Ratones , Ratones Noqueados , Regiones Promotoras Genéticas/genética , Timina ADN Glicosilasa/deficiencia , Timina ADN Glicosilasa/genéticaRESUMEN
Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), is produced in the human stomach. Although ghrelin has therapeutic potential for cancer cachexia, ghrelin treatment may have a concern about accelerating cancer progression. Here, using the human lung adenocarcinoma cell line HLC-1, we investigated the effects of ghrelin on molecular mechanisms linked to cancer progression, including cell viability, proliferation, resistance to apoptosis, and mitochondrial activity. Both types of mouse alveolar epithelial cells (types I and II) expressed the GHSR, as did the human normal airway cell lines BEAS-2B and HLC-1. Treatment with ghrelin (10-2, 10-1, 1, 10 µM) did not affect cell viability or proliferation. Pretreatment of HLC-1 cells with ghrelin (10 µM) did not affect resistance to paclitaxel-induced apoptosis. The parameters of mitochondrial respiration, including basal respiration, proton leak, ATP production, maximal respiration, spare respiratory capacity, and non-mitochondrial respiration, of the HLC-1 cells pretreated with or without ghrelin were unchanged. Taken together, ghrelin does not influence cancer progression in lung adenocarcinoma cells.
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Adenocarcinoma/patología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ghrelina/uso terapéutico , Neoplasias Pulmonares/patología , Adenocarcinoma/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Progresión de la Enfermedad , Ghrelina/administración & dosificación , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Mitocondrias/efectos de los fármacosRESUMEN
The coordination polymerization of silyl-protected ω-alkenols such as ω-alken-α-oxytriisopropylsilanes 1 provides poly(ω-alkenyl-α-oxytriisopropylsilalne)s with a highly isospecific microstructure ([mmmm] > 95%) when a combination of [OSSO]-type bis(phenolato) dichloro zirconium(IV) complex 2 and dried methylaluminoxane is used as the precatalyst and activator, respectively. The resulting siloxy-substituted polymers could be efficiently transformed into the corresponding functionalized polyolefins, which contained up to 90% acetyl groups and ≈7% hydroxy groups in the terminal side chains.
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Alcoholes/química , Compuestos Organometálicos/química , Circonio/química , Catálisis , Estructura Molecular , Compuestos Organometálicos/síntesis química , PolimerizacionRESUMEN
Back Cover: Highly isospecific polymerization of silyl-protected ω-alkenols, using a combination of [OSSO]-type bis(phenolato) dichloro zirconium(IV) complex and dMAO as the precatalyst and the activator, respectively, is established. This method represents the first example for a stereoselective polymerization of polar functional α-olefins ([mmmm] > 95%). Subsequently, the obtained terminal siloxy-substituted isotactic polymer could be readily transformed by a macromolecular desilylation/acetylation reaction sequence to afford the corresponding terminal acetyl-enriched polymer. Further details can be found in the article by Y. Saito, N. Nakata,* and A. Ishii* on page 969.
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Immunoglobulin G (IgG) antibodies are involved in type II and type III hypersensitivity. We evaluated the relation between perennial allergic conjunctivitis and serum levels of specific IgG for cat allergens. A prospective study was conducted in patients with seasonal allergic conjunctivitis (seasonal group, n = 10), patients with perennial allergic conjunctivitis (perennial group, n = 10), and healthy control subjects (control group, n = 10). Serum levels of specific IgE and IgG for cat allergens and total tear IgE were measured, and a skin prick test was also performed. In addition, a severity score associated with allergic conjunctivitis was calculated (0-30). The positive rates and scores of for total tear IgE, serum cat-specific IgE, and serum cat-specific IgG were all higher in the seasonal and perennial groups than in the control group (all p < 0.05). Serum cat-specific IgG levels were higher in the perennial group than in the seasonal group (p = 0.0156), but there was no significant difference in the grade of cat-specific IgE between the two groups (p = 0.3008). On multivariate analysis, the mean wheal diameter for cat allergen was associated with the serum level of cat-specific IgG (not IgE) in all patients [odds ratio (OR) = 31.979, p < 0.0001]. Multivariate analysis revealed that the total objective score was strongly associated with serum cat-specific IgG (OR = 23.015, p < 0.0001). These findings suggest that specific IgG antibodies may be involved in perennial allergic symptoms caused by indoor allergens such as cat allergens.
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Alérgenos/inmunología , Conjuntivitis Alérgica/inmunología , Inmunoglobulina G/sangre , Adolescente , Adulto , Animales , Estudios de Casos y Controles , Gatos , Niño , Preescolar , Conjuntivitis Alérgica/diagnóstico , Estudios Transversales , Femenino , Humanos , Inmunoglobulina E/análisis , Inmunoglobulina E/inmunología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Lágrimas/inmunología , Adulto JovenRESUMEN
Acute myeloid leukemia (AML) with high ecotropic viral integration site-1 (EVI1) expression (EVI1high AML) is classified as a refractory leukemia with a poor prognosis. We identified G protein-coupled receptor 56 (GPR56) as a novel marker for EVI1high AML, which is an orphan adhesion G protein-coupled receptor (GPCR). GPR56 was found to be associated with high cell adhesion and anti-apoptotic activities in EVI1high AML through activation of RhoA signaling. Moreover, in Gpr56-/- mice, the number of hematopoietic stem cells (HSCs) in bone marrow was significantly decreased with proportional increases in the spleen and peripheral blood, reflecting extramedullary hematopoiesis. The number of Gpr56-/- HSC progenitor cells in the G0 phase was significantly reduced with impaired adhesion and the loss of GPR56 function, which diminished the in vivo repopulating ability of HSCs. In conclusion, GPR56 may represent an important GPCR for the maintenance of quiescence and cellular adhesion of EVI1high AML and HSCs in the bone marrow niche. Moreover, given that GPR56 expression in leukemia stem cells is much higher than that in HSCs, GPR56 is a candidate therapeutic target for leukemia stem cells in EVI1high AML.