Different spectra of recurrent gene mutations in subsets of
chronic lymphocytic leukemia harboring stereotyped B-cell
receptors

J 2016

Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors

SUTTON, Lesley-Ann; Emma YOUNG; Panagiotis BALIAKAS; Anastasia HADZIDIMITRIOU; Theodoros MOYSIADIS et al.

Základní údaje

Originální název

Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors

Autoři

Vydání

Haematologica, PAVIA, FERRATA STORTI FOUNDATION, 2016, 0390-6078

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Itálie

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 7.702

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/16:00090992

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

ANTIGEN RECEPTORS; GENOMIC ABERRATIONS; EXPRESSION PROFILES; SF3B1; SELECTION; TP53; CLL; SUBGROUPS; INDICATE; PATTERNS

Štítky

MEDGENET, rivok

Změněno: 6. 12. 2016 13:27, Mgr. Eva Špillingová

Anotace

V originále

We report on markedly different frequencies of genetic lesions within subsets of chronic lymphocytic leukemia patients carrying mutated or unmutated stereotyped B-cell receptor immunoglobulins in the largest cohort (n=565) studied for this purpose. By combining data on recurrent gene mutations (BIRC3, MYD88, NOTCH1, SF3B1 and TP53) and cytogenetic aberrations, we reveal a subset-biased acquisition of gene mutations. More specifically, the frequency of NOTCH1 mutations was found to be enriched in subsets expressing unmutated immunoglobulin genes, i.e. #1, #6, #8 and #59 (22-34%), often in association with trisomy 12, and was significantly different (P<0.001) to the frequency observed in subset #2 (4%, aggressive disease, variable somatic hypermutation status) and subset #4 (1%, indolent disease, mutated immunoglobulin genes). Interestingly, subsets harboring a high frequency of NOTCH1 mutations were found to carry few (if any) SF3B1 mutations. This starkly contrasts with subsets #2 and #3 where, despite their immunogenetic differences, SF3B1 mutations occurred in 45% and 46% of cases, respectively. In addition, mutations within TP53, whilst enriched in subset #1 (16%), were rare in subsets# 2 and #8 (both 2%), despite all being clinically aggressive. All subsets were negative for MYD88 mutations, whereas BIRC3 mutations were infrequent. Collectively, this striking bias and skewed distribution of mutations and cytogenetic aberrations within specific chronic lymphocytic leukemia subsets implies that the mechanisms underlying clinical aggressiveness are not uniform, but rather support the existence of distinct genetic pathways of clonal evolution governed by a particular stereotyped B-cell receptor selecting a certain molecular lesion(s).

Návaznosti

ED1.1.00/02.0068, projekt VaV

Název: CEITEC - central european institute of technology

Citovat

SUTTON, Lesley-Ann; Emma YOUNG; Panagiotis BALIAKAS; Anastasia HADZIDIMITRIOU; Theodoros MOYSIADIS; Karla PLEVOVÁ; Davide ROSSI; Jana KMÍNKOVÁ; Evangelia STALIKA; Lone Bredo PEDERSEN; Jitka MALČÍKOVÁ; Andreas AGATHANGELIDIS; Zadie DAVIS; Larry MANSOURI; Lydia SCARFO; Myriam BOUDJOGHRA; Alba NAVARRO; Alice F. MUGGEN; Xiao-Jie YAN; Florence NGUYEN-KHAC; Marta LARRAYOZ; Panagiotis PANAGIOTIDIS; Nicholas CHIORAZZI; Carsten Utoft NIEMANN; Chrysoula BELESSI; Elias CAMPO; Jonathan C. STREFFORD; Anton W. LANGERAK; David OSCIER; Gianluca GAIDANO; Šárka POSPÍŠILOVÁ; Frederic DAVI; Paolo GHIA; Kostas STAMATOPOULOS a Richard ROSENQUIST. Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors. Haematologica. PAVIA: FERRATA STORTI FOUNDATION, 2016, roč. 101, č. 8, s. 959-967. ISSN 0390-6078. Dostupné z: https://doi.org/10.3324/haematol.2016.141812.

@article{1355432,
   author = {Sutton, LesleyandAnn and Young, Emma and Baliakas, Panagiotis and Hadzidimitriou, Anastasia and Moysiadis, Theodoros and Plevová, Karla and Rossi, Davide and Kmínková, Jana and Stalika, Evangelia and Pedersen, Lone Bredo and Malčíková, Jitka and Agathangelidis, Andreas and Davis, Zadie and Mansouri, Larry and Scarfo, Lydia and Boudjoghra, Myriam and Navarro, Alba and Muggen, Alice F. and Yan, XiaoandJie and NguyenandKhac, Florence and Larrayoz, Marta and Panagiotidis, Panagiotis and Chiorazzi, Nicholas and Niemann, Carsten Utoft and Belessi, Chrysoula and Campo, Elias and Strefford, Jonathan C. and Langerak, Anton W. and Oscier, David and Gaidano, Gianluca and Pospíšilová, Šárka and Davi, Frederic and Ghia, Paolo and Stamatopoulos, Kostas and Rosenquist, Richard},
   article_location = {PAVIA},
   article_number = {8},
   doi = {https://doi.org/10.3324/haematol.2016.141812},
   keywords = {ANTIGEN RECEPTORS; GENOMIC ABERRATIONS; EXPRESSION PROFILES; SF3B1; SELECTION; TP53; CLL; SUBGROUPS; INDICATE; PATTERNS},
   language = {eng},
   issn = {0390-6078},
   journal = {Haematologica},
   title = {Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors},
   url = {http://www.haematologica.org/content/101/8/959.full.pdf+html},
   volume = {101},
   year = {2016}
}

TY  - JOUR
ID  - 1355432
AU  - Sutton, Lesley-Ann - Young, Emma - Baliakas, Panagiotis - Hadzidimitriou, Anastasia - Moysiadis, Theodoros - Plevová, Karla - Rossi, Davide - Kmínková, Jana - Stalika, Evangelia - Pedersen, Lone Bredo - Malčíková, Jitka - Agathangelidis, Andreas - Davis, Zadie - Mansouri, Larry - Scarfo, Lydia - Boudjoghra, Myriam - Navarro, Alba - Muggen, Alice F. - Yan, Xiao-Jie - Nguyen-Khac, Florence - Larrayoz, Marta - Panagiotidis, Panagiotis - Chiorazzi, Nicholas - Niemann, Carsten Utoft - Belessi, Chrysoula - Campo, Elias - Strefford, Jonathan C. - Langerak, Anton W. - Oscier, David - Gaidano, Gianluca - Pospíšilová, Šárka - Davi, Frederic - Ghia, Paolo - Stamatopoulos, Kostas - Rosenquist, Richard
PY  - 2016
TI  - Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors
JF  - Haematologica
VL  - 101
IS  - 8
SP  - 959-967
EP  - 959-967
PB  - FERRATA STORTI FOUNDATION
SN  - 03906078
KW  - ANTIGEN RECEPTORS
KW  - GENOMIC ABERRATIONS
KW  - EXPRESSION PROFILES
KW  - SF3B1
KW  - SELECTION
KW  - TP53
KW  - CLL
KW  - SUBGROUPS
KW  - INDICATE
KW  - PATTERNS
UR  - http://www.haematologica.org/content/101/8/959.full.pdf+html
L2  - http://www.haematologica.org/content/101/8/959.full.pdf+html
N2  - We report on markedly different frequencies of genetic lesions within subsets of chronic lymphocytic leukemia patients carrying mutated or unmutated stereotyped B-cell receptor immunoglobulins in the largest cohort (n=565) studied for this purpose. By combining data on recurrent gene mutations (BIRC3, MYD88, NOTCH1, SF3B1 and TP53) and cytogenetic aberrations, we reveal a subset-biased acquisition of gene mutations. More specifically, the frequency of NOTCH1 mutations was found to be enriched in subsets expressing unmutated immunoglobulin genes, i.e. #1, #6, #8 and #59 (22-34%), often in association with trisomy 12, and was significantly different (P<0.001) to the frequency observed in subset #2 (4%, aggressive disease, variable somatic hypermutation status) and subset #4 (1%, indolent disease, mutated immunoglobulin genes). Interestingly, subsets harboring a high frequency of NOTCH1 mutations were found to carry few (if any) SF3B1 mutations. This starkly contrasts with subsets #2 and #3 where, despite their immunogenetic differences, SF3B1 mutations occurred in 45% and 46% of cases, respectively. In addition, mutations within TP53, whilst enriched in subset #1 (16%), were rare in subsets# 2 and #8 (both 2%), despite all being clinically aggressive. All subsets were negative for MYD88 mutations, whereas BIRC3 mutations were infrequent. Collectively, this striking bias and skewed distribution of mutations and cytogenetic aberrations within specific chronic lymphocytic leukemia subsets implies that the mechanisms underlying clinical aggressiveness are not uniform, but rather support the existence of distinct genetic pathways of clonal evolution governed by a particular stereotyped B-cell receptor selecting a certain molecular lesion(s).
ER  -

SUTTON, Lesley-Ann; Emma YOUNG; Panagiotis BALIAKAS; Anastasia HADZIDIMITRIOU; Theodoros MOYSIADIS; Karla PLEVOVÁ; Davide ROSSI; Jana KMÍNKOVÁ; Evangelia STALIKA; Lone Bredo PEDERSEN; Jitka MALČÍKOVÁ; Andreas AGATHANGELIDIS; Zadie DAVIS; Larry MANSOURI; Lydia SCARFO; Myriam BOUDJOGHRA; Alba NAVARRO; Alice F. MUGGEN; Xiao-Jie YAN; Florence NGUYEN-KHAC; Marta LARRAYOZ; Panagiotis PANAGIOTIDIS; Nicholas CHIORAZZI; Carsten Utoft NIEMANN; Chrysoula BELESSI; Elias CAMPO; Jonathan C. STREFFORD; Anton W. LANGERAK; David OSCIER; Gianluca GAIDANO; Šárka POSPÍŠILOVÁ; Frederic DAVI; Paolo GHIA; Kostas STAMATOPOULOS a Richard ROSENQUIST. Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors. \textit{Haematologica}. PAVIA: FERRATA STORTI FOUNDATION, 2016, roč.~101, č.~8, s.~959-967. ISSN~0390-6078. Dostupné z: https://doi.org/10.3324/haematol.2016.141812.

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