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Improved classification of leukemic B-cell lymphoproliferative disorders using a transcriptional and genetic classifier.

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journal contribution
posted on 23.08.2019, 15:32 by A Navarro, G Clot, A Martínez-Trillos, M Pinyol, P Jares, B González-Farré, D Martínez, N Trim, V Fernández, N Villamor, D Colomer, D Costa, I Salaverria, D Martín-Garcia, W Erber, C López, S Jayne, R Siebert, MJS Dyer, A Wiestner, WH Wilson, M Aymerich, A López-Guillermo, À Sánchez, E Campo, E Matutes, S Beà
B-cell chronic lymphoproliferative disorders (B-CLPD) encompass a group of hematologic tumors that often present with leukemic involvement.1 Their heterogeneity and the lack of relatively specific diagnostic markers for most of these diseases make their diagnosis challenging, especially in cases that only have blood involvement or when histology is not available. With the currently used immunophenotypic and molecular markers, around 10% of B-CLPD cases remain unclassifiable and are categorized as B-CLPD, not otherwise specified (B-CLPD, NOS). Few recurrent gene mutations and chromosomal abnormalities have been documented in some entities: BRAF and MYD88 mutations in hairy cell leukemia (HCL) and lymphoplasmacytic lymphoma (LPL), respectively,2,3 in addition to the recurrent 7q31–q32 deletion in splenic marginal zone lymphoma (SMZL).1 However, none of them are diagnostic hallmarks of any particular entity. Gene expression profiling studies have recognized specific signatures that identify most common hematological neoplasms.4,5 Based on these results we postulated that the analysis of the gene expression profiling (GEP) of a large series of leukemic B-CLPD could identify specific signatures for each leukemic disease entity. These signatures could be useful for the classification of cases with undetermined diagnosis (B-CLPD, NOS). In this study, we have investigated the GEP of a large series of leukemic lymphoid neoplasms and identified specific gene signatures for most entities that were validated in an independent cohort. We have also derived and validated a simplified quantitative polymerase chain reaction (qPCR)-based 8-gene assay that reliably recognized these entities and could assist in the diagnosis in routine practice, particularly in atypical cases and B-CLPD, NOS.

Funding

Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III PI14/00571 (SB), Fundació La Marató de TV3 TV3-Cancer/2013410 (SB), Ministerio de Economía y Competitividad, Grant No. SAF2015- 64885-R (EC), MTM2015-64465-C2-1-R (AS), Generalitat de Catalunya Suport Grups de Recerca 2013-SGR-378 (SB), 2013- SGR-0795 (EC), 2014SGR967 (DC), and 2014-SGR-464 (AS), and the European Regional Development Fund “Una manera de fer Europa”, CERCA Programme / Generalitat de Catalunya. EC is an Academia Researcher of the "Institució Catalana de Recerca i Estudis Avançats" of the Generalitat de Catalunya.

History

Citation

Haematologica, 102 (9), pp. e360-e363

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Cancer Research Centre

Version

VoR (Version of Record)

Published in

Haematologica

Publisher

Ferrata Storti Foundation

eissn

1592-8721

Copyright date

2017

Available date

23/08/2019

Notes

Supplementary figures are available from the publisher website at http://www.haematologica.org/content/102/9/e360.figures-only

Language

en