Molecular heterogeneity in chronic lymphocytic leukemia is dependent on bcr signaling: clinical correlation

ABSTRACT Chronic lymphocytic leukemia (CLL), the most frequent form of adult leukemia in Western countries, is characterized by a highly variable clinical course. Expression profiling of a

series of 160 CLL patients allowed interrogating the genes presumably playing a role in pathogenesis, relating the expression of functionally relevant signatures with the time to treatment.

First, we identified genes relevant to the biology and prognosis of CLL to build a CLL disease-specific oligonucleotide microarray. Second, we hybridized a training series on the

CLL-specific chip, generating a biology-based predictive model. Finally, this model was validated in a new CLL series. Clinical variability in CLL is related with the expression of two gene

clusters, associated with B-cell receptor (BCR) signaling and mitogen-activated protein kinase (MAPK) activation, including nuclear factor-_κ_B1 (NF-_κ_B1). The expression of these clusters

identifies three risk-score groups with treatment-free survival probabilities at 5 years of 83, 50 and 17%. This molecular predictor can be applied to early clinical stages of CLL. This

signature is related to immunoglobulin variable region somatic hypermutation and surrogate markers. There is a molecular heterogeneity in CLL, dependent on the expression of genes defining

BCR and MAPK/NF-_κ_B clusters, which can be used to predict time to treatment in early clinical stages. Access through your institution Buy or subscribe This is a preview of subscription

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LEUKEMIA AND ITS IMPACT ON OUTCOME Article 04 August 2022 GENETIC AND TRANSCRIPTOMIC ANALYSES OF DIFFUSE LARGE B-CELL LYMPHOMA PATIENTS WITH POOR OUTCOMES WITHIN TWO YEARS OF DIAGNOSIS

Article Open access 29 December 2023 MOLECULAR PATTERNS IDENTIFY DISTINCT SUBCLASSES OF MYELOID NEOPLASIA Article Open access 30 May 2023 ACCESSION CODES ACCESSIONS GENBANK/EMBL/DDBJ *

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coordination of shipment of samples. Francisco Cifuentes is a full-time employee of the company Agilent Technologies, whose custom product ‘8-pack microarray’ platform was used in the

present study. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Molecular Pathology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain A Rodríguez, R Villuendas, P de la Cueva, M C

Marín, A Swat & M A Piris * Hematology Department, Hospital Marqués de Valdecilla, Santander, Spain L Yáñez, M A Cuadrado & E Conde * Hematology Department, Hospital Gregorio

Marañón, Madrid, Spain M E Gómez & N Hernández * Bioinformatic Program, Spanish National Cancer Centre (CNIO), Madrid, Spain R Díaz * National Centre for Epidemiology, Carlos III

Institute of Health, Madrid, Spain M Pollán * Genetics and Pathology Department, Hospital Virgen de la Salud, Toledo, Spain E Ruiz * Biotechnology Program, Spanish National Cancer Centre

(CNIO), Madrid, Spain L Lombardía * Agilent Technologies, Palo Alto, CA, USA F Cifuentes * Hematology Department, Hospital Clínico Universitario, Salamanca, Spain M Gonzalez * Hematology

Department, Hospital Universitario Puerta de Hierro, Madrid, Spain J A García-Marco Authors * A Rodríguez View author publications You can also search for this author inPubMed Google Scholar

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CENTRE (CNIO) CORRESPONDING AUTHOR Correspondence to M A Piris. ADDITIONAL INFORMATION _Financial support_: This study was supported by grants from the Ministerio de Sanidad y Consumo

(G03/179, PI051623) and the Ministerio de Ciencia y Tecnología (SAF2005-00221, SAF2004-04286), Spain. Antonia Rodríguez was supported by a grant from the Asociación Española Contra el Cáncer

(AECC). Supplementary Information accompanies the paper on the Leukemia web site (http://www.nature.com/leu) SUPPLEMENTARY INFORMATION SUPPLEMENTARY FIGURE 1 (PPT 42 KB) SUPPLEMENTARY

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(XLS 464 KB) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Rodríguez, A., Villuendas, R., Yáñez, L. _et al._ Molecular heterogeneity in chronic

lymphocytic leukemia is dependent on BCR signaling: clinical correlation. _Leukemia_ 21, 1984–1991 (2007). https://doi.org/10.1038/sj.leu.2404831 Download citation * Received: 12 December

2006 * Revised: 28 May 2007 * Accepted: 30 May 2007 * Published: 05 July 2007 * Issue Date: September 2007 * DOI: https://doi.org/10.1038/sj.leu.2404831 SHARE THIS ARTICLE Anyone you share

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Nature SharedIt content-sharing initiative KEYWORDS * CLL * pathogenesis * prognosis * BCR * microarray