High-density screening reveals a different spectrum of genomic aberrations in chronic lymphocytic leukemia patients with 'stereotyped' IGHV3-21 and IGHV4-34 B-cell receptors

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High-density screening reveals a different spectrum of genomic aberrations in chronic lymphocytic leukemia patients with 'stereotyped' IGHV3-21 and IGHV4-34 B-cell receptors. / Marincevic, Millaray; Cahill, Nicola; Gunnarsson, Rebeqa; Isaksson, Anders; Mansouri, Mahmoud; Goransson, Hanna; Rasmussen, Markus; Jansson, Mattias; Ryan, Fergus; Karlsson, Karin; Adami, Hans-Olov; Davi, Fred; Jurlander, Jesper; Juliusson, Gunnar; Stamatopoulos, Kostas; Rosenquist, Richard.

I: Haematologica, Vol. 95, Nr. 9, 2010, s. 1519-1525.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Marincevic, M, Cahill, N, Gunnarsson, R, Isaksson, A, Mansouri, M, Goransson, H, Rasmussen, M, Jansson, M, Ryan, F, Karlsson, K, Adami, H-O, Davi, F, Jurlander, J, Juliusson, G, Stamatopoulos, K & Rosenquist, R 2010, 'High-density screening reveals a different spectrum of genomic aberrations in chronic lymphocytic leukemia patients with 'stereotyped' IGHV3-21 and IGHV4-34 B-cell receptors', Haematologica, vol. 95, nr. 9, s. 1519-1525. https://doi.org/10.3324/haematol.2009.021014

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CBE

Marincevic M, Cahill N, Gunnarsson R, Isaksson A, Mansouri M, Goransson H, Rasmussen M, Jansson M, Ryan F, Karlsson K, Adami H-O, Davi F, Jurlander J, Juliusson G, Stamatopoulos K, Rosenquist R. 2010. High-density screening reveals a different spectrum of genomic aberrations in chronic lymphocytic leukemia patients with 'stereotyped' IGHV3-21 and IGHV4-34 B-cell receptors. Haematologica. 95(9):1519-1525. https://doi.org/10.3324/haematol.2009.021014

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Marincevic, Millaray ; Cahill, Nicola ; Gunnarsson, Rebeqa ; Isaksson, Anders ; Mansouri, Mahmoud ; Goransson, Hanna ; Rasmussen, Markus ; Jansson, Mattias ; Ryan, Fergus ; Karlsson, Karin ; Adami, Hans-Olov ; Davi, Fred ; Jurlander, Jesper ; Juliusson, Gunnar ; Stamatopoulos, Kostas ; Rosenquist, Richard. / High-density screening reveals a different spectrum of genomic aberrations in chronic lymphocytic leukemia patients with 'stereotyped' IGHV3-21 and IGHV4-34 B-cell receptors. I: Haematologica. 2010 ; Vol. 95, Nr. 9. s. 1519-1525.

RIS

TY - JOUR

T1 - High-density screening reveals a different spectrum of genomic aberrations in chronic lymphocytic leukemia patients with 'stereotyped' IGHV3-21 and IGHV4-34 B-cell receptors

AU - Marincevic, Millaray

AU - Cahill, Nicola

AU - Gunnarsson, Rebeqa

AU - Isaksson, Anders

AU - Mansouri, Mahmoud

AU - Goransson, Hanna

AU - Rasmussen, Markus

AU - Jansson, Mattias

AU - Ryan, Fergus

AU - Karlsson, Karin

AU - Adami, Hans-Olov

AU - Davi, Fred

AU - Jurlander, Jesper

AU - Juliusson, Gunnar

AU - Stamatopoulos, Kostas

AU - Rosenquist, Richard

PY - 2010

Y1 - 2010

N2 - Background The existence of multiple subsets of chronic lymphocytic leukemia expressing 'stereotyped' B-cell receptors implies the involvement of antigen(s) in leukemogenesis. Studies also indicate that 'stereotypy' may influence the clinical course of patients with chronic lymphocytic leukemia, for example, in subsets with stereotyped IGHV3-21 and IGHV4-34 B-cell receptors; however, little is known regarding the genomic profile of patients in these subsets. Design and Methods We applied 250K single nucleotide polymorphism-arrays to study copy-number aberrations and copy-number neutral loss-of-heterozygosity in patients with stereotyped IGHV3-21 (subset #2, n=29), stereotyped IGHV4-34 (subset #4, n=17; subset #16, n=8) and non-subset #2 ICHV3-21 (n=13) and non-subset #4/16 IGHV4-34 (n=34) patients. Results Over 90% of patients in subset #2 and non-subset #2 carried copy-number aberrations, whereas 75-76% of patients in subset #4 and subset #16 showed copy-number aberrations. Subset #2 and non-subset #2 patients also displayed a higher average number of aberrations compared to patients in subset #4. Deletion of 13q was the only known recurrent aberration detected in subset #4 (35%); this aberration was even more frequent in subset #2 (79%). del(11q) was more frequent in subset #2 and non-subset #2 (31% and 23%) patients than in subset #4 and non-subset #4/16 patients. Recurrent copy-number neutral loss-of-heterozygosity was mainly detected on chromosome 13q, independently of B-cell receptor stereotypy. Conclusions Genomic aberrations were more common in subset #2 and non-subset #2 than in subset #4. The particularly high frequency of del(11q) in subset #2 may be linked to the adverse outcome reported for patients in this subset. Conversely, the lower prevalence of copy-number aberrations and the absence of poor-prognostic aberrations in subset #4 may reflect an inherently low-proliferative disease, which would prevent accumulation of genomic alterations.

AB - Background The existence of multiple subsets of chronic lymphocytic leukemia expressing 'stereotyped' B-cell receptors implies the involvement of antigen(s) in leukemogenesis. Studies also indicate that 'stereotypy' may influence the clinical course of patients with chronic lymphocytic leukemia, for example, in subsets with stereotyped IGHV3-21 and IGHV4-34 B-cell receptors; however, little is known regarding the genomic profile of patients in these subsets. Design and Methods We applied 250K single nucleotide polymorphism-arrays to study copy-number aberrations and copy-number neutral loss-of-heterozygosity in patients with stereotyped IGHV3-21 (subset #2, n=29), stereotyped IGHV4-34 (subset #4, n=17; subset #16, n=8) and non-subset #2 ICHV3-21 (n=13) and non-subset #4/16 IGHV4-34 (n=34) patients. Results Over 90% of patients in subset #2 and non-subset #2 carried copy-number aberrations, whereas 75-76% of patients in subset #4 and subset #16 showed copy-number aberrations. Subset #2 and non-subset #2 patients also displayed a higher average number of aberrations compared to patients in subset #4. Deletion of 13q was the only known recurrent aberration detected in subset #4 (35%); this aberration was even more frequent in subset #2 (79%). del(11q) was more frequent in subset #2 and non-subset #2 (31% and 23%) patients than in subset #4 and non-subset #4/16 patients. Recurrent copy-number neutral loss-of-heterozygosity was mainly detected on chromosome 13q, independently of B-cell receptor stereotypy. Conclusions Genomic aberrations were more common in subset #2 and non-subset #2 than in subset #4. The particularly high frequency of del(11q) in subset #2 may be linked to the adverse outcome reported for patients in this subset. Conversely, the lower prevalence of copy-number aberrations and the absence of poor-prognostic aberrations in subset #4 may reflect an inherently low-proliferative disease, which would prevent accumulation of genomic alterations.

KW - antigens

KW - chronic lymphocytic leukemia

KW - stereotyped B-cell receptors

KW - leukemogenesis.

U2 - 10.3324/haematol.2009.021014

DO - 10.3324/haematol.2009.021014

M3 - Article

VL - 95

SP - 1519

EP - 1525

JO - Haematologica-The Hematology Journal

T2 - Haematologica-The Hematology Journal

JF - Haematologica-The Hematology Journal

SN - 1592-8721

IS - 9

ER -