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

Baliakas, Panagiotis ; Moysiadis, Theodoros ; Hadzidimitriou, Anastasia ; Xochelli, Aliki ; Jeromin, Sabine ; Agathangelidis, Andreas ; Mattsson, Mattias ; Sutton, Lesley Ann ; Minga, Eva and Scarfò, Lydia , et al. (2019) In Haematologica 104(2). p.360-369
Abstract

Chronic lymphocytic leukemia (CLL) patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinico-biological differences. Considering this, we assessed prognosis separately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet A M-CLL 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 five and ten years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited... (More)

Chronic lymphocytic leukemia (CLL) patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinico-biological differences. Considering this, we assessed prognosis separately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet A M-CLL 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 five and ten 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 U-CLL patients, besides TP53 abnormalities, del(11q) and/or SF3B1 mutations were associated with the shortest time-to-first-treatment (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 CLL 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 CLL.

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published
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Haematologica
volume
104
issue
2
pages
10 pages
publisher
Ferrata Storti Foundation
external identifiers
  • pmid:30262567
  • scopus:85061029438
ISSN
1592-8721
DOI
10.3324/haematol.2018.195032
language
English
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yes
id
5d2077f0-1ddb-4387-bedd-5d50b87c515f
date added to LUP
2019-02-11 14:10:49
date last changed
2020-06-03 04:48:11
@article{5d2077f0-1ddb-4387-bedd-5d50b87c515f,
  abstract     = {<p>Chronic lymphocytic leukemia (CLL) patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinico-biological differences. Considering this, we assessed prognosis separately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet A M-CLL 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 five and ten 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 U-CLL patients, besides TP53 abnormalities, del(11q) and/or SF3B1 mutations were associated with the shortest time-to-first-treatment (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 CLL 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 CLL.</p>},
  author       = {Baliakas, Panagiotis and Moysiadis, Theodoros and Hadzidimitriou, Anastasia and Xochelli, Aliki and Jeromin, Sabine and Agathangelidis, Andreas and Mattsson, Mattias and Sutton, Lesley Ann and Minga, Eva and Scarfò, Lydia and Rossi, Davide and Davis, Zadie and Villamor, Neus and Parker, Helen and Kotaskova, Jana and Stalika, Evangelia and Plevova, Karla and Mansouri, Larry and Cortese, Diego and Navarro, Alba and Delgado, Julio and Larrayoz, Marta and Young, Emma and Anagnostopoulos, Achilles and Smedby, Karin E. and Juliusson, Gunnar and Sheehy, Oonagh and Catherwood, Mark and Strefford, Jonathan C. and Stavroyianni, Niki and Belessi, Chrysoula and Pospisilova, Sarka and Oscier, David and Gaidano, Gianluca and Campo, Elias and Haferlach, Claudia and Ghia, Paolo and Rosenquist, Richard and Stamatopoulos, Kostas},
  issn         = {1592-8721},
  language     = {eng},
  number       = {2},
  pages        = {360--369},
  publisher    = {Ferrata Storti Foundation},
  series       = {Haematologica},
  title        = {Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia},
  url          = {http://dx.doi.org/10.3324/haematol.2018.195032},
  doi          = {10.3324/haematol.2018.195032},
  volume       = {104},
  year         = {2019},
}