Background: A variety of surrogate markers for genetic features and outcome have been described in chronic lymphocytic leukemia based on gene expression analyses. Previous studies mostly focused on individual markers and selected disease characteristics, which makes it difficult to estimate the relative value of the novel markers. Therefore, in the present study a comprehensive approach was chosen investigating 18 promising, partly novel expression markers in a well characterized cohort of patients with long clinical follow-up and full genetic information (IGHV status, genomic abnormalities). Design and Methods: Expression markers were evaluated using real-time quantitative reverse transcriptase polymerase chain reaction in CD19+-purified samples from 151 patients. Multivariate analyses were performed to test the markers' ability to identify patients at genetic risk and as prognostic markers in the context of established prognostic factors. Results: For individual markers, ZAP70 expression provided the highest rate (81%) of correct assignment of patients at genetic risk (IGHV unmutated, V3-21 usage, 11q- or 17p-), followed by LPL and TCF7 (76% both). The assignment rate was improved to 88% by information from a four-gene combination (ZAP70, TCF7, DMD, ATM). In multivariate analysis of treatment-free survival, IGHV mutation status and expression of ADAM29 were of independent prognostic value besides disease stage. With regards to overall survival, expression of ATM, ADAM29, TCL1, and SEPT10 provided prognostic information in addition to that derived from clinical and genetic factors. Conclusions: Gene expression markers are suitable for screening but not as surrogates for the information from genetic risk factors. While many individual markers may be associated with out-come, only a few are of independent prognostic significance. With regard to prognosis estimation, the genetic prognostic factors cannot be replaced by the expression markers.

Deregulation of MIR-221/222 cluster affects P27 expression in multiple myeloma / M. Lionetti, D. Verdelli, D. Ronchetti, R.L. Nobili, L. Agnelli, L. Lombardi, G. Lambertenghi Deliliers, A. Neri. - In: HAEMATOLOGICA. - ISSN 0390-6078. - 95:suppl. 3(2010), pp. S102-S103. ((Intervento presentato al 11. convegno Congress of the Italian Society of Experimental Hematology tenutosi a Torino nel 2010.

Deregulation of MIR-221/222 cluster affects P27 expression in multiple myeloma

M. Lionetti
Primo
;
D. Verdelli
Secondo
;
D. Ronchetti;R.L. Nobili;L. Agnelli;G. Lambertenghi Deliliers
Penultimo
;
A. Neri
Ultimo
2010

Abstract

Background: A variety of surrogate markers for genetic features and outcome have been described in chronic lymphocytic leukemia based on gene expression analyses. Previous studies mostly focused on individual markers and selected disease characteristics, which makes it difficult to estimate the relative value of the novel markers. Therefore, in the present study a comprehensive approach was chosen investigating 18 promising, partly novel expression markers in a well characterized cohort of patients with long clinical follow-up and full genetic information (IGHV status, genomic abnormalities). Design and Methods: Expression markers were evaluated using real-time quantitative reverse transcriptase polymerase chain reaction in CD19+-purified samples from 151 patients. Multivariate analyses were performed to test the markers' ability to identify patients at genetic risk and as prognostic markers in the context of established prognostic factors. Results: For individual markers, ZAP70 expression provided the highest rate (81%) of correct assignment of patients at genetic risk (IGHV unmutated, V3-21 usage, 11q- or 17p-), followed by LPL and TCF7 (76% both). The assignment rate was improved to 88% by information from a four-gene combination (ZAP70, TCF7, DMD, ATM). In multivariate analysis of treatment-free survival, IGHV mutation status and expression of ADAM29 were of independent prognostic value besides disease stage. With regards to overall survival, expression of ATM, ADAM29, TCL1, and SEPT10 provided prognostic information in addition to that derived from clinical and genetic factors. Conclusions: Gene expression markers are suitable for screening but not as surrogates for the information from genetic risk factors. While many individual markers may be associated with out-come, only a few are of independent prognostic significance. With regard to prognosis estimation, the genetic prognostic factors cannot be replaced by the expression markers.
Settore MED/15 - Malattie del Sangue
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/147832
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact