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Transcription profiling by array of human CD34+ cells from bone marrow of patients with mucosa-associated lymphoid tissue (MLAT) lymphoma and control CD34+ cells from healthy individuals

ABSTRACT: Comparison of gene expression profiling analysis of bone marrow isolated CD34+ cells from patients with MALT lymphoma vs. healthy individuals revealed a large number of differentially expressed genes that included NF-kB target genes, genes involved in inflamatory signalling and immunoglobulin genes, suggesting an early lymphoid B-cell priming. Chromosomal translocations involving MALT1 gene are hallmarks of mucosa-associated lymphoid tissue (MALT) lymphoma. However, targeting these translocations to mouse B-cells has failed to reproduce human disease. Here, we induced MALT1 expression in mouse Sca1+Lin- hematopoietic stem/progenitor cells (HS/PCs), leading to the development of tumors recapitulating the clinical, histopathological and molecular features of human MALT lymphomas. Ablation of the p53 gene induced transformation of MALT lymphoma to diffuse large-cell lymphoma of activated B-cell type (ABC-DLBCL). Human CD34+ cells isolated from MALT lymphoma patients displayed an abnormal transcriptional program that was shared by MALT lymphoma cells, transgenic mouse Sca1+Lin- cells and Sca1-MALT1-induced lymphomas. Our study shows that MALT lymphoma can be modeled in mice by targeting MALT1 oncogene to HS/PCs. 10 samples were analyzed of which 5 are CD34+ cells sorted from the bone marrow of MALT patients and are compared to the other 5 CD34+ cells sorted from the bone marrow of healthy donors.


ORGANISM(S): Homo sapiens  

PROVIDER: E-GEOD-34015 | ExpressionAtlas | 2014-07-03

REPOSITORIES: ExpressionAtlas

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Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.

Vicente-Dueñas Carolina C   Fontán Lorena L   Gonzalez-Herrero Ines I   Romero-Camarero Isabel I   Segura Victor V   Aznar M Angela MA   Alonso-Escudero Esther E   Campos-Sanchez Elena E   Ruiz-Roca Lucía L   Barajas-Diego Marcos M   Sagardoy Ainara A   Martinez-Ferrandis Jose I JI   Abollo-Jimenez Fernando F   Bertolo Cristina C   Peñuelas Ivan I   Garcia-Criado Francisco J FJ   García-Cenador María B MB   Tousseyn Thomas T   Agirre Xabier X   Prosper Felipe F   Garcia-Bragado Federico F   McPhail Ellen D ED   Lossos Izidore S IS   Du Ming-Qing MQ   Flores Teresa T   Hernandez-Rivas Jesus M JM   Gonzalez Marcos M   Salar Antonio A   Bellosillo Beatriz B   Conde Eulogio E   Siebert Reiner R   Sagaert Xavier X   Cobaleda Cesar C   Sanchez-Garcia Isidro I   Martinez-Climent Jose A JA  

Proceedings of the National Academy of Sciences of the United States of America 20120611 26

Chromosomal translocations involving the MALT1 gene are hallmarks of mucosa-associated lymphoid tissue (MALT) lymphoma. To date, targeting these translocations to mouse B cells has failed to reproduce human disease. Here, we induced MALT1 expression in mouse Sca1(+)Lin(-) hematopoietic stem/progenitor cells, which showed NF-κB activation and early lymphoid priming, being selectively skewed toward B-cell differentiation. These cells accumulated in extranodal tissues and gave rise to clonal tumors  ...[more]

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