Surrogate molecular markers for IGHV mutational status in chronic lymphocytic leukemia for predicting time to first treatment

Fortunato Morabito, Giovanna Cutrona, Laura Mosca, Marianna D'Anca, Serena Matis, Massimo Gentile, Ernesto Vigna, Monica Colombo, Anna Grazia Recchia, Sabrina Bossio, Laura De Stefano, Francesco Maura, Martina Manzoni, Fiorella Ilariucci, Ugo Consoli, Iolanda Vincelli, Caterina Musolino, Agostino Cortelezzi, Stefano Molica, Manlio FerrariniAntonino Neri

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

ZAP-70 is a marker of clinical outcome in chronic lymphocytic leukemia (CLL), however its assessment suffers from a lack of standardization consensus. To identify novel markers able to surrogate IGHV mutational status, CD19(+)CD5(+)- B-lymphocytes from 216 patients enrolled in a prospective study (ClinicalTrial.gov Identifier:. NCT00917540), underwent gene expression profiling. Samples were split into CLL-Training ( n = 102) and CLL-Validation ( n = 114) sets, and an independent supervised analysis for IGHV mutational status was performed considering all genes with gene expression equal or above that of ZAP-70. Thirty-one genes (23 up- and 8 down-regulated) and 23 genes (18 up- and 5 down-regulated) satisfied these criteria in the CLL-Training and CLL-Validation sets, respectively, and 20 common genes (15 up and 5 down) were found to be differentially regulated in both sets. Two (SNORA70F, NRIP1) of the down-regulated and 6 (SEPT10, ZNF667, TGFBR3, MBOAT1, LPL, CRY1) of the up-regulated genes were significantly associated with a reduced risk of disease progression in both sets. Forcing the afore-mentioned genes in a Cox multivariate model together with IGHV mutational status, only CRY1 (HR = 2.3, 95% CI: 1.1-4.9, P = .027) and MBOAT1 (HR = 2.1, 95% CI: 1.1-3.7, P = .018) retained their independent prognostic impact, supporting the hypothesis that these genes may potentially act as surrogates for predicting IGHV mutational status.

Original languageEnglish
Pages (from-to)840-845
Number of pages6
JournalLeukemia Research
Volume39
Issue number8
DOIs
Publication statusPublished - Aug 1 2015

Fingerprint

B-Cell Chronic Lymphocytic Leukemia
Biomarkers
Genes
Therapeutics
Gene Expression Profiling
Proportional Hazards Models
Disease Progression
B-Lymphocytes
Prospective Studies
Gene Expression

Keywords

  • Chronic lymphocytic leukemia
  • CRY1
  • Flow-cytometry
  • Gene expression profiling
  • IGHV
  • MBOAT1
  • Prognostic markers
  • Progression free survival
  • SNORA70F
  • ZAP-70

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology
  • Medicine(all)

Cite this

Surrogate molecular markers for IGHV mutational status in chronic lymphocytic leukemia for predicting time to first treatment. / Morabito, Fortunato; Cutrona, Giovanna; Mosca, Laura; D'Anca, Marianna; Matis, Serena; Gentile, Massimo; Vigna, Ernesto; Colombo, Monica; Recchia, Anna Grazia; Bossio, Sabrina; De Stefano, Laura; Maura, Francesco; Manzoni, Martina; Ilariucci, Fiorella; Consoli, Ugo; Vincelli, Iolanda; Musolino, Caterina; Cortelezzi, Agostino; Molica, Stefano; Ferrarini, Manlio; Neri, Antonino.

In: Leukemia Research, Vol. 39, No. 8, 01.08.2015, p. 840-845.

Research output: Contribution to journalArticle

Morabito, F, Cutrona, G, Mosca, L, D'Anca, M, Matis, S, Gentile, M, Vigna, E, Colombo, M, Recchia, AG, Bossio, S, De Stefano, L, Maura, F, Manzoni, M, Ilariucci, F, Consoli, U, Vincelli, I, Musolino, C, Cortelezzi, A, Molica, S, Ferrarini, M & Neri, A 2015, 'Surrogate molecular markers for IGHV mutational status in chronic lymphocytic leukemia for predicting time to first treatment', Leukemia Research, vol. 39, no. 8, pp. 840-845. https://doi.org/10.1016/j.leukres.2015.05.005
Morabito, Fortunato ; Cutrona, Giovanna ; Mosca, Laura ; D'Anca, Marianna ; Matis, Serena ; Gentile, Massimo ; Vigna, Ernesto ; Colombo, Monica ; Recchia, Anna Grazia ; Bossio, Sabrina ; De Stefano, Laura ; Maura, Francesco ; Manzoni, Martina ; Ilariucci, Fiorella ; Consoli, Ugo ; Vincelli, Iolanda ; Musolino, Caterina ; Cortelezzi, Agostino ; Molica, Stefano ; Ferrarini, Manlio ; Neri, Antonino. / Surrogate molecular markers for IGHV mutational status in chronic lymphocytic leukemia for predicting time to first treatment. In: Leukemia Research. 2015 ; Vol. 39, No. 8. pp. 840-845.
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AU - Vigna, Ernesto

AU - Colombo, Monica

AU - Recchia, Anna Grazia

AU - Bossio, Sabrina

AU - De Stefano, Laura

AU - Maura, Francesco

AU - Manzoni, Martina

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AU - Consoli, Ugo

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AU - Musolino, Caterina

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