Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations

Panagiotis Baliakas; Andreas Agathangelidis; Anastasia Hadzidimitriou; Lesley-Ann Sutton; Eva Minga; Athina Tsanousa; Lydia Scarfò; Zadie Davis; Xiao-Jie Yan; Tait Shanafelt; Karla Plevova; Yorick Sandberg; Fie Juhl Vojdeman; Myriam Boudjogra; Tatiana Tzenou; Maria Chatzouli; Charles C Chu; Silvio Veronese; Anne Gardiner; Larry Mansouri; Karin E Smedby; Lone Bredo Pedersen; Denis Moreno; Kirsten Van Lom; Véronique Giudicelli; Hana Skuhrova Francova; Florence Nguyen-Khac; Panagiotis Panagiotidis; Gunnar Juliusson; Lefteris Angelis; Achilles Anagnostopoulos; Marie-Paule Lefranc; Monica Facco; Livio Trentin; Mark Catherwood; Marco Montillo; Christian H Geisler; Anton W Langerak; Sarka Pospisilova; Nicholas Chiorazzi; David Oscier; Diane F Jelinek; Nikos Darzentas; Chrysoula Belessi; Frederic Davi; Paolo Ghia; Richard Rosenquist; Kostas Stamatopoulos

doi:10.1182/blood-2014-09-600874

Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations

Panagiotis Baliakas, Andreas Agathangelidis, Anastasia Hadzidimitriou, Lesley-Ann Sutton, Eva Minga, Athina Tsanousa, Lydia Scarfò, Zadie Davis, Xiao-Jie Yan, Tait Shanafelt, Karla Plevova, Yorick Sandberg, Fie Juhl Vojdeman, Myriam Boudjogra, Tatiana Tzenou, Maria Chatzouli, Charles C Chu, Silvio Veronese, Anne Gardiner, Larry MansouriKarin E Smedby, Lone Bredo Pedersen, Denis Moreno, Kirsten Van Lom, Véronique Giudicelli, Hana Skuhrova Francova, Florence Nguyen-Khac, Panagiotis Panagiotidis, Gunnar Juliusson, Lefteris Angelis, Achilles Anagnostopoulos, Marie-Paule Lefranc, Monica Facco, Livio Trentin, Mark Catherwood, Marco Montillo, Christian H Geisler, Anton W Langerak, Sarka Pospisilova, Nicholas Chiorazzi, David Oscier, Diane F Jelinek, Nikos Darzentas, Chrysoula Belessi, Frederic Davi, Paolo Ghia, Richard Rosenquist, Kostas Stamatopoulos

74 Citations (Scopus)

Abstract

An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset #2. Within subset #2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset #2/IGHV3-21 was enriched for IGHV-unmutated cases (P = .002). Subset #2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset #2/IGHV3-21 (22 vs 60 months, P = .001). No such difference was observed between non-subset #2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset #2 emerges as uniformly aggressive, contrasting non-subset #2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.

Original language	English
Journal	Blood
Volume	125
Issue number	5
Pages (from-to)	856-9
Number of pages	4
ISSN	0006-4971
DOIs	https://doi.org/10.1182/blood-2014-09-600874
Publication status	Published - 29 Jan 2015

Keywords

Aged
Antineoplastic Agents
B-Lymphocytes
Female
Gene Expression Regulation, Leukemic
Gene Rearrangement, B-Lymphocyte, Heavy Chain
Genetic Heterogeneity
Humans
Immunoglobulin Heavy Chains
Leukemia, Lymphocytic, Chronic, B-Cell
Male
Middle Aged
Prognosis
Somatic Hypermutation, Immunoglobulin
Survival Analysis
Time-to-Treatment
Treatment Outcome

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Baliakas, P., Agathangelidis, A., Hadzidimitriou, A., Sutton, L.-A., Minga, E., Tsanousa, A., Scarfò, L., Davis, Z., Yan, X.-J., Shanafelt, T., Plevova, K., Sandberg, Y., Vojdeman, F. J., Boudjogra, M., Tzenou, T., Chatzouli, M., Chu, C. C., Veronese, S., Gardiner, A., ... Stamatopoulos, K. (2015). Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations. Blood, 125(5), 856-9. https://doi.org/10.1182/blood-2014-09-600874

Baliakas, P, Agathangelidis, A, Hadzidimitriou, A, Sutton, L-A, Minga, E, Tsanousa, A, Scarfò, L, Davis, Z, Yan, X-J, Shanafelt, T, Plevova, K, Sandberg, Y, Vojdeman, FJ, Boudjogra, M, Tzenou, T, Chatzouli, M, Chu, CC, Veronese, S, Gardiner, A, Mansouri, L, Smedby, KE, Pedersen, LB, Moreno, D, Van Lom, K, Giudicelli, V, Francova, HS, Nguyen-Khac, F, Panagiotidis, P, Juliusson, G, Angelis, L, Anagnostopoulos, A, Lefranc, M-P, Facco, M, Trentin, L, Catherwood, M, Montillo, M, Geisler, CH, Langerak, AW, Pospisilova, S, Chiorazzi, N, Oscier, D, Jelinek, DF, Darzentas, N, Belessi, C, Davi, F, Ghia, P, Rosenquist, R & Stamatopoulos, K 2015, 'Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations', Blood, vol. 125, no. 5, pp. 856-9. https://doi.org/10.1182/blood-2014-09-600874

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title = "Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations",

abstract = "An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset #2. Within subset #2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset #2/IGHV3-21 was enriched for IGHV-unmutated cases (P = .002). Subset #2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset #2/IGHV3-21 (22 vs 60 months, P = .001). No such difference was observed between non-subset #2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset #2 emerges as uniformly aggressive, contrasting non-subset #2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.",

keywords = "Aged, Antineoplastic Agents, B-Lymphocytes, Female, Gene Expression Regulation, Leukemic, Gene Rearrangement, B-Lymphocyte, Heavy Chain, Genetic Heterogeneity, Humans, Immunoglobulin Heavy Chains, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Middle Aged, Prognosis, Somatic Hypermutation, Immunoglobulin, Survival Analysis, Time-to-Treatment, Treatment Outcome",

author = "Panagiotis Baliakas and Andreas Agathangelidis and Anastasia Hadzidimitriou and Lesley-Ann Sutton and Eva Minga and Athina Tsanousa and Lydia Scarf{\`o} and Zadie Davis and Xiao-Jie Yan and Tait Shanafelt and Karla Plevova and Yorick Sandberg and Vojdeman, {Fie Juhl} and Myriam Boudjogra and Tatiana Tzenou and Maria Chatzouli and Chu, {Charles C} and Silvio Veronese and Anne Gardiner and Larry Mansouri and Smedby, {Karin E} and Pedersen, {Lone Bredo} and Denis Moreno and {Van Lom}, Kirsten and V{\'e}ronique Giudicelli and Francova, {Hana Skuhrova} and Florence Nguyen-Khac and Panagiotis Panagiotidis and Gunnar Juliusson and Lefteris Angelis and Achilles Anagnostopoulos and Marie-Paule Lefranc and Monica Facco and Livio Trentin and Mark Catherwood and Marco Montillo and Geisler, {Christian H} and Langerak, {Anton W} and Sarka Pospisilova and Nicholas Chiorazzi and David Oscier and Jelinek, {Diane F} and Nikos Darzentas and Chrysoula Belessi and Frederic Davi and Paolo Ghia and Richard Rosenquist and Kostas Stamatopoulos",

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doi = "10.1182/blood-2014-09-600874",

language = "English",

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journal = "Blood",

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T1 - Not all IGHV3-21 chronic lymphocytic leukemias are equal

T2 - prognostic considerations

AU - Baliakas, Panagiotis

AU - Agathangelidis, Andreas

AU - Hadzidimitriou, Anastasia

AU - Sutton, Lesley-Ann

AU - Minga, Eva

AU - Tsanousa, Athina

AU - Scarfò, Lydia

AU - Davis, Zadie

AU - Yan, Xiao-Jie

AU - Shanafelt, Tait

AU - Plevova, Karla

AU - Sandberg, Yorick

AU - Vojdeman, Fie Juhl

AU - Boudjogra, Myriam

AU - Tzenou, Tatiana

AU - Chatzouli, Maria

AU - Chu, Charles C

AU - Veronese, Silvio

AU - Gardiner, Anne

AU - Mansouri, Larry

AU - Smedby, Karin E

AU - Pedersen, Lone Bredo

AU - Moreno, Denis

AU - Van Lom, Kirsten

AU - Giudicelli, Véronique

AU - Francova, Hana Skuhrova

AU - Nguyen-Khac, Florence

AU - Panagiotidis, Panagiotis

AU - Juliusson, Gunnar

AU - Angelis, Lefteris

AU - Anagnostopoulos, Achilles

AU - Lefranc, Marie-Paule

AU - Facco, Monica

AU - Trentin, Livio

AU - Catherwood, Mark

AU - Montillo, Marco

AU - Geisler, Christian H

AU - Langerak, Anton W

AU - Pospisilova, Sarka

AU - Chiorazzi, Nicholas

AU - Oscier, David

AU - Jelinek, Diane F

AU - Darzentas, Nikos

AU - Belessi, Chrysoula

AU - Davi, Frederic

AU - Ghia, Paolo

AU - Rosenquist, Richard

AU - Stamatopoulos, Kostas

PY - 2015/1/29

Y1 - 2015/1/29

N2 - An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset #2. Within subset #2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset #2/IGHV3-21 was enriched for IGHV-unmutated cases (P = .002). Subset #2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset #2/IGHV3-21 (22 vs 60 months, P = .001). No such difference was observed between non-subset #2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset #2 emerges as uniformly aggressive, contrasting non-subset #2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.

AB - An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset #2. Within subset #2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset #2/IGHV3-21 was enriched for IGHV-unmutated cases (P = .002). Subset #2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset #2/IGHV3-21 (22 vs 60 months, P = .001). No such difference was observed between non-subset #2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset #2 emerges as uniformly aggressive, contrasting non-subset #2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.

KW - Aged

KW - Antineoplastic Agents

KW - B-Lymphocytes

KW - Female

KW - Gene Expression Regulation, Leukemic

KW - Gene Rearrangement, B-Lymphocyte, Heavy Chain

KW - Genetic Heterogeneity

KW - Humans

KW - Immunoglobulin Heavy Chains

KW - Leukemia, Lymphocytic, Chronic, B-Cell

KW - Male

KW - Middle Aged

KW - Prognosis

KW - Somatic Hypermutation, Immunoglobulin

KW - Survival Analysis

KW - Time-to-Treatment

KW - Treatment Outcome

U2 - 10.1182/blood-2014-09-600874

DO - 10.1182/blood-2014-09-600874

M3 - Journal article

C2 - 25634617

SN - 0006-4971

VL - 125

SP - 856

EP - 859

JO - Blood

JF - Blood

IS - 5

ER -

Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations

Abstract

Keywords

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