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Chronic lymphocytic leukemia

Significance of chromosome 2p gain in ibrutinib-treated chronic lymphocytic leukemia patients

Leukemia volume 35, pages 3287–3290 (2021)Cite this article

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Gain or amplification of the short arm of chromosome 2 (2p) is a recurrent cytogenetic abnormality in B-lymphoid disorders including chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL) [1, 2]. 2p gain can extend across the whole chromosome arm, or encompass only a minimally gained region of ~1.3 Mb [3]. A number of genes in the 2p region are important to B-cell development as well as oncogenesis, and have been postulated as important targets within this gain. These include the proto-oncogene MYCN in chromosome band 2p24.3, and the NFKB subunit REL, nuclear transporter XPO1, and proto-oncogene BCL11A within the minimally gained chromosomal region of 2p15-16.1 [3, 4].

Reports on frequency of 2p gain in CLL range from 3 to 28% in untreated patients [4, 5] and can be acquired during clonal evolution [6]. 2p gain in CLL has been previously associated with transformation to DLBCL (Richter’s transformation) [7], where it has been detected in CLL prior to transformation and afterwards within the transformed lymphoma cells [6]. Similarly, 2p gain has also been described in FL prior to and after transformation to DLBCL, as well as in de novo DLBCL, indicating that this alteration may be contributing to an aggressive B-cell phenotype [8]. 2p gain has been associated with a poor overall survival (OS) in CLL [7]; however, this association has not been consistently observed [9]. Importantly, previous studies were limited by either small numbers of patients with 2p gain or were performed when treatment for CLL predominately involved chemotherapy or chemo-immunotherapy.

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Fig. 1: Survival curves with and without 2p gain.

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Author notes

  1. These authors contributed equally: Erin K. Hertlein, Jennifer A. Woyach

Authors and Affiliations

  1. Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, USA

    Cecelia R. Miller, Lynne V. Abruzzo & Nyla A. Heerema

  2. Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA

    Ying Huang, Amy S. Ruppert, Jadwiga Labanowska, Samantha M. Jaglowski, Kami J. Maddocks, Kerry A. Rogers, Seema Bhat, Adam S. Kittai, Michael Grever, Rosa Lapalombella, John C. Byrd, Erin K. Hertlein & Jennifer A. Woyach

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Correspondence to Jennifer A. Woyach.

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Conflict of interest

KJM has received research support and has served as a consultant for Pharmacyclics. SMJ has received research funding from Pharmacyclics. JAW has served as a consultant for Janssen, Pharmacyclics, Abbvie, AstraZeneca, and Arqule, and has received research funding from Abbvie and Loxo.

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Miller, C.R., Huang, Y., Ruppert, A.S. et al. Significance of chromosome 2p gain in ibrutinib-treated chronic lymphocytic leukemia patients. Leukemia 35, 3287–3290 (2021). https://doi.org/10.1038/s41375-021-01237-x

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