Clonal dynamics monitoring during clinical evolution in chronic lymphocytic leukaemia

González-Rincón, Julia; Gómez, Sagrario; Martinez, Nerea; Troulé, Kevin; Perales-Patón, Javier; Derdak, Sophia; Beltrán, Sergi; Fernández-Cuevas, Belén; Pérez-Sanz, Nuria; Nova-Gurumeta, Sara; Gut, Marta; Al‐Shahrour, Fátima; Piris, Miguel Á.; García-Marco, José A.; Sánchez‐Beato, Margarita

doi:10.1038/s41598-018-37389-7

Cited by 8 publications

(11 citation statements)

References 35 publications

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“…Although the mechanisms at play in the pathogenesis of RS remain incompletely understood, recent endeavors may explain the evolution of RS clonally related to CLL: Gonzlez-Rincon et al [ 21 ] propose both a linear sequence of acquisition of new mutational events in a single clone, and a branched evolution, spatially and temporally heterogeneous, with the appearance of 2 or more tumoral clones, co-existing and evolving in parallel. In contrast, the clonally unrelated cases of RS may be explained by the immunosuppression caused by CLL/SLL and/or its therapy, analogous to the causal link between non-Hodgkin lymphoma and HIV infection and post-transplantation lymphoproliferative disorders.…”

Section: Discussionmentioning

confidence: 99%

Extranodal NK/T cell lymphoma and lymphomatoid granulomatosis in a patient with chronic lymphocytic leukaemia

Abi‐Rafeh¹,

Beamish²,

Haegert³

et al. 2020

Medicine

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Rationale: Richter syndrome (RS) defines the transformation of chronic lymphocytic leukemia (CLL) into a more aggressive lymphoma. Although the term RS is most often reserved for transformation of CLL into diffuse large B-cell lymphoma (DLBCL), and less frequently Hodgkin lymphoma , the list of cases with more variable presentations in the literature is growing. Patient concerns: A 71-year-old Caucasian man initially consulted an otolaryngologist for a 1-year history of nasal congestion. Diagnoses: The asynchronous occurrence of 2 rare angiocentric Epstein–Barr virus (EBV)-related lymphoproliferative disorders in a patient with CLL, specifically clonally related lymphomatoid granulomatosis (LYG), and an extranodal NK/T-cell lymphoma, nasal type, are described herein. Interventions: Radiation therapy and a regimen of cis-platinum were administered for the NK/T cell lymphoma, and ibrutinib for LYG. Outcomes: The patient remains in complete clinical remission 8 years after the diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma and recurrent extranodal NK/T cell lymphoma, and 2 years after the diagnosis of clonally related LYG. Lessons: Although the precise pathogenesis of RS remains incompletely understood, various molecular alterations, in particular long-term immunosuppression, may lead to RS, similar to the causal link existing between non-Hodgkin lymphomas and HIV infection, and post-transplantation lymphoproliferative disorders. EBV infection is linked to the pathogenesis of several types of lymphomas and found in a subset of patients with RS; immunosuppression, in the context of CLL or other pathological conditions or pharmacological agents, can disrupt the fine balance between virus and the host immune system, and result in EBV-driven lymphoproliferations of B-, T-, or NK-cell origin. The findings of our literature review thus suggest that such non-diffuse large B-cell lymphoma , non-Hodgkin lymphoma CLL transformations, may be considered as rare variants of RS.

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Section: Discussionmentioning

confidence: 99%

Extranodal NK/T cell lymphoma and lymphomatoid granulomatosis in a patient with chronic lymphocytic leukaemia

Abi‐Rafeh¹,

Beamish²,

Haegert³

et al. 2020

Medicine

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“…On the contrary, the median survival of patients with clonally related RS is significantly shorter, ranging from 8 to 14 months [6]. Clonal dynamics monitoring of clonal unrelated RS has demonstrated clonal evolution, acquiring and selecting new mutations in response to treatment, and loss of cellular tumoral clone during progression [26].…”

Section: Discussionmentioning

confidence: 99%

The Occurrence of Richter’s Syndrome during Treatment with Obinutuzumab and Chlorambucil

Carnley

Green

et al. 2020

Case Reports in Hematology

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Chronic lymphocytic leukaemia is a slow-growing leukaemia of developing B-lymphocytes, which may transform to an aggressive lymphoma known as Richter’s syndrome. While Richter’s syndrome can present in untreated or relapsed-refractory cases, it may occur upon the commencement of less intensity treatment regimens. We present a case of Richter’s syndrome following treatment with chlorambucil and obinutuzumab and review of available literature on the topic.

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“…Subsequently, we tested our models on longitudinal genomic data involving a higher number of timepoints. The first dataset comes from Patient 1 in [24]. A total of 13 peripheral blood mononuclear cell samples (P1.1 to P1.13) were collected over the course of 6.5 years and underwent targeted sequencing (TGS).…”

Section: The Case Of Patient Cll003mentioning

confidence: 99%

“…In return, we obtain a continuous reconstruction of the time course of each cluster during the course of the disease from a small number of sequentially collected samples. We test various model configurations on whole genome (WGS), whole exome (WES) and targeted sequencing (TGS) data from patients with chronic lymphocytic leukaemia (CLL; [23,24]), on data from the liquid biopsy of a patient with melanoma [25] and on synthetic data, and we demonstrate that incorporating temporal information in our analysis can boost the performance of clonal deconvolution.…”

Section: Introductionmentioning

confidence: 99%

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A statistical approach for tracking clonal dynamics in cancer using longitudinal next-generation sequencing data

Vavoulis

Cutts

Taylor

et al. 2020

Preprint

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Tumours are composed of genotypically and phenotypically distinct cancer cell populations (clones), which are subject to a process of Darwinian evolution in response to changes in their local microenvironment, such as drug treatment. In a cancer patient, this process of continuous adaptation can be studied through next-generation sequencing of multiple tumour samples combined with appropriate bioinformatics and statistical methodologies. One family of statistical methods for clonal deconvolution seeks to identify groups of mutations and estimate the prevalence of each group in the tumour, while taking into account its purity and copy number profile. These methods have been used in the analysis of cross-sectional data, as well as for longitudinal data by discarding information on the timing of sample collection. Two key questions are how (in the case of longitudinal data) can we incorporate such information in our analyses and if there is any benefit in doing so. Regarding the first question, we incorporated information on the temporal spacing of longitudinally collected samples into standard non-parametric approaches for clonal deconvolution by modelling the time dependence of the prevalence of each clone as a Gaussian process. This permitted reconstruction of the temporal profile of the abundance of each clone continuously from several sparsely collected samples and without any strong prior assumptions on the functional form of this profile. Regarding the second question, we tested various model configurations on a range of whole genome, whole exome and targeted sequencing data from patients with chronic lymphocytic leukaemia, on liquid biopsy data from a patient with melanoma and on synthetic data. We demonstrate that incorporating temporal information in our analysis improves model performance, as long as data of sufficient volume and complexity are available for estimating free model parameters. We expect that our approach will be useful in cases where collecting a relatively long sequence of tumour samples is feasible, as in the case of liquid cancers (e.g. leukaemia) and liquid biopsies. The statistical methodology presented in this paper is freely available at github.com/dvav/clonosGP.

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Clonal dynamics monitoring during clinical evolution in chronic lymphocytic leukaemia

Cited by 8 publications

References 35 publications

Extranodal NK/T cell lymphoma and lymphomatoid granulomatosis in a patient with chronic lymphocytic leukaemia

Extranodal NK/T cell lymphoma and lymphomatoid granulomatosis in a patient with chronic lymphocytic leukaemia

The Occurrence of Richter’s Syndrome during Treatment with Obinutuzumab and Chlorambucil

A statistical approach for tracking clonal dynamics in cancer using longitudinal next-generation sequencing data

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