Multiple productive immunoglobulin heavy chain gene
rearrangements in chronic lymphocytic leukemia are mostly
derived from independent clones

J 2014

Multiple productive immunoglobulin heavy chain gene rearrangements in chronic lymphocytic leukemia are mostly derived from independent clones

PLEVOVÁ, Karla, Hana SKUHROVÁ FRANCOVÁ, Kateřina BURČKOVÁ, Yvona BRYCHTOVÁ, Michael DOUBEK et. al.

Basic information

Original name

Multiple productive immunoglobulin heavy chain gene rearrangements in chronic lymphocytic leukemia are mostly derived from independent clones

Authors

PLEVOVÁ, Karla (203 Czech Republic, belonging to the institution), Hana SKUHROVÁ FRANCOVÁ (203 Czech Republic, belonging to the institution), Kateřina BURČKOVÁ (203 Czech Republic, belonging to the institution), Yvona BRYCHTOVÁ (203 Czech Republic, belonging to the institution), Michael DOUBEK (203 Czech Republic, belonging to the institution), Šárka PAVLOVÁ (203 Czech Republic, belonging to the institution), Jitka MALČÍKOVÁ (203 Czech Republic, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution), Boris TICHÝ (203 Czech Republic, belonging to the institution) and Šárka POSPÍŠILOVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Haematologica, Pavia (Italy), FERRATA STORTI FOUNDATION, 2014, 0390-6078

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30200 3.2 Clinical medicine

Country of publisher

Italy

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 5.814

RIV identification code

RIV/00216224:14740/14:00077731

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.3324/haematol.2013.087593

UT WoS

000336253900026

Keywords in English

Chronic lymphocytic leukemia; immunoglobulin; B lymphocyte

Abstract

V originále

In chronic lymphocytic leukemia, usually a monoclonal disease, multiple productive immunoglobulin heavy chain gene rearrangements are identified sporadically. Prognostication of such cases based on immunoglobulin heavy variable gene mutational status can be problematic, especially if the different rearrangements have discordant mutational status. To gain insight into the possible biological mechanisms underlying the origin of the multiple rearrangements, we performed a comprehensive immunogenetic and immunophenotypic characterization of 31 cases with the multiple rearrangements identified in a cohort of 1147 patients with chronic lymphocytic leukemia. For the majority of cases (25/31), we provide evidence of the co-existence of at least two B lymphocyte clones with a chronic lymphocytic leukemia phenotype. We also identified clonal drifts in serial samples, likely driven by selection forces. More specifically, higher immunoglobulin variable gene identity to germline and longer complementarity determining region 3 were preferred in persistent or newly appearing clones, a phenomenon more pronounced in patients with stereotyped B-cell receptors. Finally, we report that other factors, such as TP53 gene defects and therapy administration, influence clonal selection. Our findings are relevant to clonal evolution in the context of antigen stimulation and transition of monoclonal B-cell lymphocytosis to chronic lymphocytic leukemia.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

EE2.3.20.0045, research and development project

Name: Podpora profesního růstu a mezinárodní integrace výzkumných týmů v oblasti molekulární medicíny

MUNI/A/0723/2012, interní kód MU

Name: Nové klinické a diagnostické přístupy u hematogických malignit (Acronym: NoKliDiPřiHeMa)

Investor: Masaryk University, Category A

NT13493, research and development project

Name: Molekulární charakterizace B buněčných receptorů a jejich vztah k evoluci genetických změn u chronické lymfocytární leukémie

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Cite

PLEVOVÁ, Karla, Hana SKUHROVÁ FRANCOVÁ, Kateřina BURČKOVÁ, Yvona BRYCHTOVÁ, Michael DOUBEK, Šárka PAVLOVÁ, Jitka MALČÍKOVÁ, Jiří MAYER, Boris TICHÝ and Šárka POSPÍŠILOVÁ. Multiple productive immunoglobulin heavy chain gene rearrangements in chronic lymphocytic leukemia are mostly derived from independent clones. Haematologica. Pavia (Italy): FERRATA STORTI FOUNDATION, 2014, vol. 99, No 2, p. 329-338. ISSN 0390-6078. Available from: https://dx.doi.org/10.3324/haematol.2013.087593.

@article{1212648,
   author = {Plevová, Karla and Skuhrová Francová, Hana and Burčková, Kateřina and Brychtová, Yvona and Doubek, Michael and Pavlová, Šárka and Malčíková, Jitka and Mayer, Jiří and Tichý, Boris and Pospíšilová, Šárka},
   article_location = {Pavia (Italy)},
   article_number = {2},
   doi = {http://dx.doi.org/10.3324/haematol.2013.087593},
   keywords = {Chronic lymphocytic leukemia; immunoglobulin; B lymphocyte},
   language = {eng},
   issn = {0390-6078},
   journal = {Haematologica},
   title = {Multiple productive immunoglobulin heavy chain gene rearrangements in chronic lymphocytic leukemia are mostly derived from independent clones},
   url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912964/pdf/0990329.pdf},
   volume = {99},
   year = {2014}
}

TY  - JOUR
ID  - 1212648
AU  - Plevová, Karla - Skuhrová Francová, Hana - Burčková, Kateřina - Brychtová, Yvona - Doubek, Michael - Pavlová, Šárka - Malčíková, Jitka - Mayer, Jiří - Tichý, Boris - Pospíšilová, Šárka
PY  - 2014
TI  - Multiple productive immunoglobulin heavy chain gene rearrangements in chronic lymphocytic leukemia are mostly derived from independent clones
JF  - Haematologica
VL  - 99
IS  - 2
SP  - 329-338
EP  - 329-338
PB  - FERRATA STORTI FOUNDATION
SN  - 03906078
KW  - Chronic lymphocytic leukemia
KW  - immunoglobulin
KW  - B lymphocyte
UR  - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912964/pdf/0990329.pdf
L2  - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912964/pdf/0990329.pdf
N2  - In chronic lymphocytic leukemia, usually a monoclonal disease, multiple productive immunoglobulin heavy chain gene rearrangements are identified sporadically. Prognostication of such cases based on immunoglobulin heavy variable gene mutational status can be problematic, especially if the different rearrangements have discordant mutational status. To gain insight into the possible biological mechanisms underlying the origin of the multiple rearrangements, we performed a comprehensive immunogenetic and immunophenotypic characterization of 31 cases with the multiple rearrangements identified in a cohort of 1147 patients with chronic lymphocytic leukemia. For the majority of cases (25/31), we provide evidence of the co-existence of at least two B lymphocyte clones with a chronic lymphocytic leukemia phenotype. We also identified clonal drifts in serial samples, likely driven by selection forces. More specifically, higher immunoglobulin variable gene identity to germline and longer complementarity determining region 3 were preferred in persistent or newly appearing clones, a phenomenon more pronounced in patients with stereotyped B-cell receptors. Finally, we report that other factors, such as TP53 gene defects and therapy administration, influence clonal selection. Our findings are relevant to clonal evolution in the context of antigen stimulation and transition of monoclonal B-cell lymphocytosis to chronic lymphocytic leukemia.
ER  -

PLEVOVÁ, Karla, Hana SKUHROVÁ FRANCOVÁ, Kateřina BURČKOVÁ, Yvona BRYCHTOVÁ, Michael DOUBEK, Šárka PAVLOVÁ, Jitka MALČÍKOVÁ, Jiří MAYER, Boris TICHÝ and Šárka POSPÍŠILOVÁ. Multiple productive immunoglobulin heavy chain gene rearrangements in chronic lymphocytic leukemia are mostly derived from independent clones. \textit{Haematologica}. Pavia (Italy): FERRATA STORTI FOUNDATION, 2014, vol.~99, No~2, p.~329-338. ISSN~0390-6078. Available from: https://dx.doi.org/10.3324/haematol.2013.087593.

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