| Autoři |
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
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| Rok publikování |
2016 |
| Druh |
Článek v odborném periodiku
|
| Časopis / Zdroj |
Haematologica |
| Fakulta / Pracoviště MU |
Středoevropský technologický institut
|
| Citace |
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://dx.doi.org/10.3324/haematol.2016.141812. |
| www |
http://www.haematologica.org/content/101/8/959.full.pdf+html
|
| Doi |
http://dx.doi.org/10.3324/haematol.2016.141812 |
| Obor |
Onkologie a hematologie |
| Klíčová slova |
ANTIGEN RECEPTORS; GENOMIC ABERRATIONS; EXPRESSION PROFILES; SF3B1; SELECTION; TP53; CLL; SUBGROUPS; INDICATE; PATTERNS
|
| Popis |
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).
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