title: Two distinct molecular subtypes of chronic lymphocytic leukemia give new insights on the pathogenesis of the disease and identify novel therapeutic targets.
abstract: Biopsy samples of lymph nodes from 38 patients with CLL were analyzed. We found differential expression in 1092 genes in two different subgroups: 418 overexpressed in one subgroup and 674 in another. Molecular pathways identified in one subgroup appear to be characterized by greater dependence of signaling by cytokines and activation of the NFkB pathway, while in the other seem to depend on cell cycle. Despite having found a differential expression between both subgroups, none of these genes reached FDR < 0.25. We have not found significant association with survival or any prognostic factors. Analysis of the differences between normal lymph node and CLL in 253 genes with difference in the intensity of expression revealed upregulated genes different to BCR: CD40, TCL1, IL-7, and PAX5. Using large-scale molecular analysis, we may obtain information about molecular mechanisms of CLL pathogenesis and may contribute to the identification of new therapeutic targets.
authors: a Lymphoma Unit, Fundacion Jimenez Diaz University Hospital, Health Research Institute IIS-FJD , Madrid , Spain.
authors: Raul
authors: R
authors: Cordoba
authors: b Health Research Institute, Hospital Universitario Puerta de Hierro Majadahonda , Madrid , Spain.|c Lymphoma Group, Spanish National Cancer Research Center (CNIO) , Madrid , Spain.
authors: Margarita
authors: M
authors: Sanchez-Beato
authors: c Lymphoma Group, Spanish National Cancer Research Center (CNIO) , Madrid , Spain.
authors: Beatriz
authors: B
authors: Herreros
authors: c Lymphoma Group, Spanish National Cancer Research Center (CNIO) , Madrid , Spain.
authors: Elena
authors: E
authors: Domenech
authors: b Health Research Institute, Hospital Universitario Puerta de Hierro Majadahonda , Madrid , Spain.
authors: Jose
authors: J
authors: Garcia-Marco
authors: d Pathology Department, MD Anderson Cancer Center , Madrid , Spain.
authors: Juan-F
authors: JF
authors: Garcia
authors: e Hematology Department, Hospital Universitario Doce de Octubre , Madrid , Spain.
authors: Joaquin
authors: J
authors: Martinez-Lopez
authors: e Hematology Department, Hospital Universitario Doce de Octubre , Madrid , Spain.
authors: Antonia
authors: A
authors: Rodriguez
authors: a Lymphoma Unit, Fundacion Jimenez Diaz University Hospital, Health Research Institute IIS-FJD , Madrid , Spain.
authors: Aranzazu
authors: A
authors: Garcia-Raso
authors: a Lymphoma Unit, Fundacion Jimenez Diaz University Hospital, Health Research Institute IIS-FJD , Madrid , Spain.
authors: Pilar
authors: P
authors: Llamas
authors: c Lymphoma Group, Spanish National Cancer Research Center (CNIO) , Madrid , Spain.|f Research Institute Marques de Valdecilla (IDIVAL) , Santander , Spain.
authors: Miguel-Angel
authors: MA
authors: Piris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001706:Biopsy; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor
keywords: Chronic lymphocytic leukemia; gene-expression profile; molecular subtype