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A Retinoic Acid-dependent Stroma-Leukemia Crosstalk Promotes Chronic Lymphocytic Leukemia Progression [RNA-seq]

ABSTRACT: In B-cell chronic lymphocytic leukemia (CLL), the non-hematopoietic stromal microenvironment plays a critical role in promoting tumor cell recruitment, activation, survival and expansion. Using the Eμ-TCL1 mouse model, we demonstrate that leukemic cells induce the activation of retinoid acid synthesis and signaling in stromal cells of the lymphoid microenvironment.

OTHER RELATED OMICS DATASETS IN: PRJNA437128PRJNA437512PRJNA437532

ORGANISM(S): Mus musculus

PROVIDER: GSE111612 | GEO | 2018/05/09

REPOSITORIES: GEO

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A Retinoic Acid-dependent Stroma-Leukemia Crosstalk Promotes Chronic Lymphocytic Leukemia Progression [microarray]

Project description:In B-cell chronic lymphocytic leukemia (CLL), the non-hematopoietic stromal microenvironment plays a critical role in promoting tumor cell recruitment, activation, survival and expansion. Using the Eμ-TCL1 mouse model, we demonstrate that leukemic cells induce the activation of retinoid acid synthesis and signaling in stromal cells of the lymphoid microenvironment.

2018-05-09 | GSE111470 | GEO

A retinoic acid-dependent stroma-leukemia crosstalk promotes chronic lymphocytic leukemia progression.

Project description:In chronic lymphocytic leukemia (CLL), the non-hematopoietic stromal microenvironment plays a critical role in promoting tumor cell recruitment, activation, survival, and expansion. However, the nature of the stromal cells and molecular pathways involved remain largely unknown. Here, we demonstrate that leukemic B lymphocytes induce the activation of retinoid acid synthesis and signaling in the microenvironment. Inhibition of RA-signaling in stromal cells causes deregulation of genes associated with adhesion, tissue organization and chemokine secretion including the B-cell chemokine CXCL13. Notably, reducing retinoic acid precursors from the diet or inhibiting RA-signaling through retinoid-antagonist therapy prolong survival by preventing dissemination of leukemia cells into lymphoid tissues. Furthermore, mouse and human leukemia cells could be distinguished from normal B-cells by their increased expression of Rarγ2 and RXRα, respectively. These findings establish a role for retinoids in murine CLL pathogenesis, and provide new therapeutic strategies to target the microenvironment and to control disease progression.

| S-EPMC5934403 | biostudies-literature

Access to follicular dendritic cells is a pivotal step in murine chronic lymphocytic leukemia B cell activation and proliferation

Project description:In human chronic lymphocytic leukemia (CLL) pathogenesis B cell antigen receptor signaling seems important for leukemia B cell ontogeny, whereas the microenvironment influences B cell activation, tumor cell lodging and provision of antigenic stimuli. Using the murine Eμ-Tcl1 CLL model, we demonstrate that CXCR5-controlled access to follicular dendritic cells (FDCs) confers proliferative stimuli to leukemia B cells. Intravital imaging revealed a marginal zone B cell-like leukemia cell trafficking route. Murine and human CLL cells reciprocally stimulated resident mesenchymal stromal cells through lymphotoxin-β-receptor activation, resulting in CXCL13 secretion and stromal compartment remodeling. Inhibition of lymphotoxin/lymphotoxin-β-receptor signaling or of CXCR5 signaling retards leukemia progression. Thus, CXCR5 activity links tumor cell homing, shaping a survival niche, and access to localized proliferation stimuli.

2014-09-01 | GSE60925 | GEO

A Retinoic Acid-dependent Stroma-Leukemia Crosstalk Promotes Chronic Lymphocytic Leukemia Progression

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-05-09 | GSE111613 | GEO

A Retinoic Acid-dependent Stroma-Leukemia Crosstalk Promotes Chronic Lymphocytic Leukemia Progression

Project description:A Retinoic Acid-dependent Stroma-Leukemia Crosstalk Promotes Chronic Lymphocytic Leukemia Progression

| PRJNA437512 | ENA

Access to follicular dendritic cells is a pivotal step in murine chronic lymphocytic leukemia B cell activation and proliferation

Project description:In human chronic lymphocytic leukemia (CLL) pathogenesis B cell antigen receptor signaling seems important for leukemia B cell ontogeny, whereas the microenvironment influences B cell activation, tumor cell lodging and provision of antigenic stimuli. Using the murine E?-Tcl1 CLL model, we demonstrate that CXCR5-controlled access to follicular dendritic cells (FDCs) confers proliferative stimuli to leukemia B cells. Intravital imaging revealed a marginal zone B cell-like leukemia cell trafficking route. Murine and human CLL cells reciprocally stimulated resident mesenchymal stromal cells through lymphotoxin-?-receptor activation, resulting in CXCL13 secretion and stromal compartment remodeling. Inhibition of lymphotoxin/lymphotoxin-?-receptor signaling or of CXCR5 signaling retards leukemia progression. Thus, CXCR5 activity links tumor cell homing, shaping a survival niche, and access to localized proliferation stimuli. This GEO dataset is comprised of GEP measurements for EµTCL mouse CD5+CD19+ tumor cells and healthy WT controls, including healthy MZB cells and B1 cells. 6 measurements are for WT EµTCL1 mice, 5 for the CXCR5-KO EµTCL1 genotype. MZB and B1 cells were pooled from 15 animals. WT reference was obtained from 5 WT animals

2014-09-01 | E-GEOD-60925 | biostudies-arrayexpress

A Retinoic Acid-dependent Stroma-Leukemia Crosstalk Promotes Chronic Lymphocytic Leukemia Progression [microarray]

Project description:A Retinoic Acid-dependent Stroma-Leukemia Crosstalk Promotes Chronic Lymphocytic Leukemia Progression [microarray]

| PRJNA437128 | ENA

A Retinoic Acid-dependent Stroma-Leukemia Crosstalk Promotes Chronic Lymphocytic Leukemia Progression [RNA-seq]

Project description:A Retinoic Acid-dependent Stroma-Leukemia Crosstalk Promotes Chronic Lymphocytic Leukemia Progression [RNA-seq]

| PRJNA437532 | ENA

Gene expression in murine chronic lymphocytic leukemia

Project description:mRNA profiles of B cells from 8-week-old wild-type (WT) and leukemic (Eu-TCL1) mice were generated by 3'-sequencing, in triplicate.

2021-09-07 | GSE175564 | GEO

Gene expression in murine chronic lymphocytic leukemia B cells (Eu-TCL1 and Eu-TCL1-Rab27DKO)

Project description:mRNA profiles of leukemic B cells from 8-week-old leukemic (Eu-TCL1 and Eu-TCL1-Rab27DKO) mice were generated by 3'-sequencing, in triplicate.

2022-08-31 | GSE190790 | GEO

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