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Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia

Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia
Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia
Chronic lymphocytic leukemia patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinicobiological differences. Considering this, we assessed prognosis separately within mutated and unmutated chronic lymphocytic leukemia in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet-A mutated chronic lymphocytic leukemia patients, besides TP53 abnormalities, trisomy 12 and stereotyped subset #2 membership were equivalently associated with the shortest time-to-first-treatment and a treatment probability at 5- and 10-years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited 5-year and 10-year treatment probability of 12% and 25%, respectively. Within Binet-A unmutated chronic lymphocytic leukemia patients, besides TP53 abnormalities, del(11q) and/or SF3B1 mutations were associated with the shortest time-to-first-trearment (5- and 10-year treatment probability: 78% and 98%, respectively); in the remaining cases, males had a significantly worse prognosis than females. In conclusion, the relative weight of indicators that can accurately risk stratify early-stage chronic lymphocytic leukemia patients differs depending on the somatic hypermutation status of the immunoglobulin heavy variable genes of each patient. This finding highlights the fact that compartmentalized approaches based on immunogenetic features are necessary to refine and tailor prognostication in chronic lymphocytic leukemia.
0390-6078
Baliakas, Panagiotis
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Xochelli, Aliki
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Mattsson, Mattias
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Minga, Eva
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Davis, Zadie
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Parker, Helen
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Kotaskova, Jana
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Delgado, Julio
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Larrayoz, Marta
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Anagnostopoulos, Achilles
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Catherwood, Mark
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Strefford, Jonathan C.
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Gaidano, Gianluca
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Campo, Elias
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Haferlach, Claudia
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Ghia, Paolo
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Rosenquist, Richard
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Stamatopoulos, Kostas
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Baliakas, Panagiotis
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Xochelli, Aliki
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Jeromin, Sabine
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Delgado, Julio
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Larrayoz, Marta
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Young, Emma
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Smedby, Karin
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Campo, Elias
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Haferlach, Claudia
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Ghia, Paolo
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Rosenquist, Richard
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Baliakas, Panagiotis, Moysiadis, Theodoros, Hadzidimitriou, Anastasia, Xochelli, Aliki, Jeromin, Sabine, Agathangelidis, Andreas, Mattsson, Mattias, Sutton, Lesley-Ann, Minga, Eva, Scarfò, Lydia, Rossi, Davide, Davis, Zadie, Villamor, Neus, Parker, Helen, Kotaskova, Jana, Delgado, Julio, Larrayoz, Marta, Young, Emma, Anagnostopoulos, Achilles, Smedby, Karin, Juliusson, Gunnar, Sheehy, Oonagh, Catherwood, Mark, Strefford, Jonathan C., Stavroyianni, Niki, Belessi, Chrysoula, Pospisilova, Sarka, Oscier, David, Gaidano, Gianluca, Campo, Elias, Haferlach, Claudia, Ghia, Paolo, Rosenquist, Richard and Stamatopoulos, Kostas (2018) Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia. Haematologica. (doi:10.3324/haematol.2018.195032).

Record type: Article

Abstract

Chronic lymphocytic leukemia patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinicobiological differences. Considering this, we assessed prognosis separately within mutated and unmutated chronic lymphocytic leukemia in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet-A mutated chronic lymphocytic leukemia patients, besides TP53 abnormalities, trisomy 12 and stereotyped subset #2 membership were equivalently associated with the shortest time-to-first-treatment and a treatment probability at 5- and 10-years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited 5-year and 10-year treatment probability of 12% and 25%, respectively. Within Binet-A unmutated chronic lymphocytic leukemia patients, besides TP53 abnormalities, del(11q) and/or SF3B1 mutations were associated with the shortest time-to-first-trearment (5- and 10-year treatment probability: 78% and 98%, respectively); in the remaining cases, males had a significantly worse prognosis than females. In conclusion, the relative weight of indicators that can accurately risk stratify early-stage chronic lymphocytic leukemia patients differs depending on the somatic hypermutation status of the immunoglobulin heavy variable genes of each patient. This finding highlights the fact that compartmentalized approaches based on immunogenetic features are necessary to refine and tailor prognostication in chronic lymphocytic leukemia.

Text
haematol.2018.195032.full - Accepted Manuscript
Available under License Creative Commons Attribution.
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Accepted/In Press date: 25 September 2018
e-pub ahead of print date: 27 September 2018
Published date: 27 September 2018

Identifiers

Local EPrints ID: 425910
URI: http://eprints.soton.ac.uk/id/eprint/425910
ISSN: 0390-6078
PURE UUID: 99ad4e0f-4d60-446a-b5fb-91888fda4aa3
ORCID for Helen Parker: ORCID iD orcid.org/0000-0001-8308-9781
ORCID for Jonathan C. Strefford: ORCID iD orcid.org/0000-0002-0972-2881

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Date deposited: 06 Nov 2018 17:30
Last modified: 30 Jan 2020 01:33

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Contributors

Author: Panagiotis Baliakas
Author: Theodoros Moysiadis
Author: Anastasia Hadzidimitriou
Author: Aliki Xochelli
Author: Sabine Jeromin
Author: Andreas Agathangelidis
Author: Mattias Mattsson
Author: Lesley-Ann Sutton
Author: Eva Minga
Author: Lydia Scarfò
Author: Davide Rossi
Author: Zadie Davis
Author: Neus Villamor
Author: Helen Parker ORCID iD
Author: Jana Kotaskova
Author: Julio Delgado
Author: Marta Larrayoz
Author: Emma Young
Author: Achilles Anagnostopoulos
Author: Karin Smedby
Author: Gunnar Juliusson
Author: Oonagh Sheehy
Author: Mark Catherwood
Author: Niki Stavroyianni
Author: Chrysoula Belessi
Author: Sarka Pospisilova
Author: David Oscier
Author: Gianluca Gaidano
Author: Elias Campo
Author: Claudia Haferlach
Author: Paolo Ghia
Author: Richard Rosenquist
Author: Kostas Stamatopoulos

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