Circulating soluble LR11/SorLA levels are highly increased and ameliorated by chemotherapy in acute leukemias

Sakai, Shio; Nakaseko, Chiaki; Takeuchi, Masahiro; Ohwada, Chikako; Shimizu, Naomi; Tsukamoto, Shokichi; Kawaguchi, Takeshi; Jiang, Meizi; Sato, Yasunori; Ebinuma, Hiroyuki; Yokote, Koutaro; Iwama, Atsushi; Fukamachi, Isamu; Schneider, Wolfgang J.; Saitō, Yasushi; Bujo, Hideaki

doi:10.1016/j.cca.2012.06.025

Cited by 25 publications

(21 citation statements)

References 29 publications

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“…Soluble LR11 (sLR11) is released through proteolytic shedding. Circulating sLR11 is a biomarker for atherosclerosis, coronary stenosis, diabetic retinopathy and acute leukemia39404142. A role for CD9 in the shedding of LR11 in leukocytes has also been reported43.…”

Section: Discussionmentioning

confidence: 99%

Genetically regulated hepatic transcripts and pathways orchestrate haematological, biochemical and body composition traits

Ponsuksili

Trakooljul

Hadlich

et al. 2016

Sci Rep

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The liver is the central metabolic organ and exhibits fundamental functions in haematological traits. Hepatic expression, haematological, plasma biochemical, and body composition traits were assessed in a porcine model (n = 297) to establish tissue-specific genetic variations that influence the function of immune-metabolism-correlated expression networks. At FDR (false discovery rate) <1%, more than 3,600 transcripts were jointly correlated (r = |0.22–0.48|) with the traits. Functional enrichment analysis demonstrated common links of metabolic and immune traits. To understand how immune and metabolic traits are affected via genetic regulation of gene expression, eQTLs were assessed. 20517 significant (FDR < 5%) eQTLs for 1401 transcripts were identified, among which 443 transcripts were associated with at least one of the examined traits and had cis-eQTL (such as ACO1 (6.52 × 10−7) and SOD1 (6.41 × 10−30). The present study establishes a comprehensive view of hepatic gene activity which links together metabolic and immune traits in a porcine model for medical research.

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Section: Discussionmentioning

confidence: 99%

Genetically regulated hepatic transcripts and pathways orchestrate haematological, biochemical and body composition traits

Ponsuksili

Trakooljul

Hadlich

et al. 2016

Sci Rep

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“…ELISA-Amounts of soluble LR11 released into the culture medium were determined by sandwich ELISA as reported previously (27). Briefly, culture media were concentrated by using Amicon Ultra-15 (100,000 NMWL membranes from Millipore), and the concentrated sample was reacted with the capture monoclonal antibody M3 and then incubated with the biotinylated reporter rat monoclonal antibody R14.…”

Section: Methodsmentioning

confidence: 99%

“…4 Zhang et al reported high levels of LR11 mRNA in human CD34 ϩ CD38 Ϫ immature hematopoietic precursors (26). Both LR11 mRNA and cell surface protein levels are elevated in immature leukemic cells, in turn leading to increased levels of sLR11 in acute leukemias (27). Thus, it is conceivable that in hypoxic environments, modulation of uPAR expression by sLR11 may be important for maintenance of the HSPC pool size.…”

mentioning

confidence: 99%

The Soluble Form of LR11 Protein Is a Regulator of Hypoxia-induced, Urokinase-type Plasminogen Activator Receptor (uPAR)-mediated Adhesion of Immature Hematological Cells

Nishii

Nakaseko

Jiang

et al. 2013

Journal of Biological Chemistry

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Background: Serum levels of the soluble LR11 fragment (sLR11) increase in patients with acute leukemia. Results: Hypoxia-induced factor (HIF)-1␣ activation increases LR11 levels, and sLR11 enhances adhesion of HSPCs to BM stromal cells via a uPAR-mediated pathway. Conclusion: sLR11 regulates hypoxia-induced attachment of HSPCs. Significance: sLR11 may stabilize the hematological pool size by controlling HSPC attachment to the BM niche.

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“…In addition, we found increased gene expression of Lr11, also referred as Sorl1, which belongs to the LDL receptor gene family. LR11 protein is highly expressed in the atheromatous plaques, particularly in vascular cells [54], and moreover, it has been demonstrated that it is expressed on the cell surface of monocytes in human PBMCs [55]. LR11 is a membrane protein with a large extracellular part, known as soluble LR11 (sLR11), which is released to circulation by proteolytic shedding and its increase in serum is considered a biomarker of pathologies related to increased adiposity as atherosclerosis [56].…”

Section: Energy Homeostasismentioning

confidence: 99%

Peripheral blood mononuclear cells as a source to detect markers of homeostatic alterations caused by the intake of diets with an unbalanced macronutrient composition

Díaz‐Rúa

Keijer

Caimari

et al. 2015

The Journal of Nutritional Biochemistry

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Circulating soluble LR11/SorLA levels are highly increased and ameliorated by chemotherapy in acute leukemias

Cited by 25 publications

References 29 publications

Genetically regulated hepatic transcripts and pathways orchestrate haematological, biochemical and body composition traits

Genetically regulated hepatic transcripts and pathways orchestrate haematological, biochemical and body composition traits

The Soluble Form of LR11 Protein Is a Regulator of Hypoxia-induced, Urokinase-type Plasminogen Activator Receptor (uPAR)-mediated Adhesion of Immature Hematological Cells

Peripheral blood mononuclear cells as a source to detect markers of homeostatic alterations caused by the intake of diets with an unbalanced macronutrient composition

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