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Series GSE154589 Query DataSets for GSE154589
Status Public on Jul 17, 2020
Title Inhibition of Inflammatory Signaling in Pax5 Mutant Cells Mitigates B-cell leukemogenesis against leukemia
Organism Mus musculus
Experiment type Expression profiling by array
Summary We used microarrays to investigate gene expression changes in healthy and leukemic cells from Pax5+/- and IL6+/-;Pax5+/- mice in CF and SPF housing conditions.
PAX5 is one of the most frequently mutated genes in B-cell acute lymphoblastic leukemia (B-ALL), and children with inherited preleukemic PAX5 mutations are at a higher risk of developing the disease. Abnormal profiles of inflammatory markers can be detected in neonatal blood spot samples of children who later developed B-cell precursor B-ALL. However, how inflammatory signals contribute to B-ALL development is unclear. Here, we demonstrate that Pax5 loss results in the enhanced production of the inflammatory cytokine interleukin-6 (IL-6), which appears to act in an autocrine fashion to promote leukemia growth. In vivo genetic downregulation of IL-6 in Pax5 mutant mice retards B-cell leukemogenesis. In vivo pharmacologic inhibition of IL-6 with a neutralizing IL-6 antibody in Pax5 mutant mice with B-ALL clears leukemic cells. This exciting novel IL 6 signaling paradigm identified in mice was also substantiated in humans. Altogether, our studies establish aberrant IL6 expression caused by Pax5 loss as a hallmark of Pax5-dependent B-ALL and the IL6 as a therapeutic vulnerability for B-ALL characterized by PAX5 loss.
 
Overall design We used microarrays to investigate gene expression changes in healthy and leukemic cells from Pax5+/- and IL6+/-;Pax5+/- mice in CF and SPF housing conditions.
 
Contributor(s) Isidro-Hernández M, Colino AM, Casado-García A, Raboso-Gallego J, Orfao A, Salas JR, Ribera JM, Zamora L, Blanco O, Alonso-López D, De Las Rivas J, Jiménez R, Criado FJ, Cenador MB, Ramírez-Orellana M, Cobaleda C, Vicente-Dueñas C, Sánchez-García I
Citation(s) 33154497
Submission date Jul 16, 2020
Last update date Nov 16, 2020
Contact name Isidro Sánchez García
E-mail(s) isg@usal.es
Organization name Inst. de Inv. Biomédica de Salamanca (IBSAL). H. U. de Salamanca. Inst. de Biología Molecular y Celular del Cáncer (IBMCC).
Department Centro de inv. del Cáncer (CIC).
Street address Campus Miguel de Unamuno
City Salamanca
ZIP/Postal code E37007
Country Spain
 
Platforms (1)
GPL6246 [MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version]
Samples (22)
GSM4675010 Bone Marrow proB and preB cells of WT mouse housed in CF, biological replicate 1
GSM4675011 Bone Marrow proB and preB cells of WT mouse housed in CF, biological replicate 2
GSM4675012 Bone Marrow proB and preB cells of WT mouse housed in CF, biological replicate 3
Relations
BioProject PRJNA646739

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Supplementary file Size Download File type/resource
GSE154589_RAW.tar 98.4 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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