IGH 3’RR recombination uncovers a non-germinal center imprint and c-MYC-dependent IGH rearrangement in unmutated chronic lymphocytic leukemia

Jamal, Israa Al; Parquet, Milene; Guiyedi, Kenza; Aoufouchi, Saïd; Guillou, Morwenna Le; Rizzo, David M.; Pollet, Justine; Dupont, Marine; Boulin, Mélanie; Faumont, Nathalie; Boutouil, Hend; Jardin, Fabrice; Ruminy, Philippe; Hamel, Chahrazed El; Lerat, J.; Hamaoui, Samar Al; Makdissy, Nehman; Feuillard, Jean; Gachard, Nathalie; Péron, Sophie

doi:10.3324/haematol.2023.282897

Cited by 2 publications

(1 citation statement)

References 52 publications

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“…AID also plays a crucial role in IGH rearrangements, specifically in processes such as class switch recombination (CSR) and recombination between switch Mu (Sµ) and the 3 ′ regulatory region (3 ′ RR) (Sµ-3 ′ RRrec). Given the predominant presence of unswitched CLL B-cells, an investigation into the blockade of IGH rearrangement in CLL was prompted [24]. Patients with somatic IGHVm with <98% germline homology are considered to have a better prognosis.…”

Section: Genetic Alterationsmentioning

confidence: 99%

Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era

Sánchez Suárez,

Martín Roldán,

Alarcón-Payer

et al. 2023

Pharmaceutics

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Chronic lymphocytic leukemia is a lymphoproliferative disorder marked by the expansion of monoclonal, mature CD5+CD23+ B cells in peripheral blood, secondary lymphoid tissues, and bone marrow. The disease exhibits significant heterogeneity, with numerous somatic genetic alterations identified in the neoplastic clone, notably mutated TP53 and immunoglobulin heavy chain mutational statuses. Recent studies emphasize the pivotal roles of genetics and patient fragility in treatment decisions. This complexity underscores the need for a personalized approach, tailoring interventions to individual genetic profiles for heightened efficacy. The era of personalized treatment in CLL signifies a transformative shift, holding the potential for improved outcomes in the conquest of this intricate hematologic disorder. This review plays a role in elucidating the evolving CLL treatment landscape, encompassing all reported genetic factors. Through a comprehensive historical analysis, it provides insights into the evolution of CLL management. Beyond its retrospective nature, this review could be a valuable resource for clinicians, researchers, and stakeholders, offering a window into the latest advancements. In essence, it serves as a dynamic exploration of our current position and the promising prospects on the horizon.

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Section: Genetic Alterationsmentioning

confidence: 99%

Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era

Sánchez Suárez,

Martín Roldán,

Alarcón-Payer

et al. 2023

Pharmaceutics

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Sµ-3’RRrecHigh Chronic Lymphocytic Leukemia is associated with specific gene expression signature, activation-induced cMYC expression and sustained cell cycle entry.

Milène,

Kenza,

Justine

et al. 2024

Preprint

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Chronic lymphocytic leukemia (CLL) is an indolent non-Hodgkin B-cell lymphoma and is still incurable. In a previous study of CLL patients, the IGH locus DNA recombination between the switch µ (Sµ) and one 3’ regulatory regions (3’RR), the Sµ-3’RRrec, was detected more frequently than in normal condition. As a reminder, the Sµ-3'RRrec has been repeatedly detected in B-cells of mice and humans and is expected to induce cell death. Sµ-3’RRrec appears to be a rare event in normal B-cells. The Sµ-3’RRrecHigh CLLs harboring high count of Sµ-3’RRrec junctions in DNA from blood samples has been characterized as a poor prognosis group with increased MYC expression. In these cases, the increase in Sµ-3'RRrec probably reflects ongoing recombination activity. In order to deepen the molecular basis involved in the IGH recombination process underway in Sµ-3'RRrecHigh CLL, we further characterized how the patient groups differ. Our results provide additional features suggesting distinct cellular response to BCR stimulation, different cell signaling and non comparable cell cycle dynamics. Briefly, the Sµ-3'RRrecHigh samples appear to retain the ability to respond to BCR stimulation, resulting in increased c-MYC expression and to fast cell cycle entry. Whereas Sµ-3'RRrecLow CLLs appear to show a lesser response to BCR stimulation and increased Bcl2 transcripts in lymph nodes that could contribute to a more indolent disease. This latter is probably associated with an attenuated genetic recombination activity. Whereas this latter must be exacerbated in condition of more intense proliferation due to MYC in Sµ-3'RRrecHigh CLL.

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IGH 3’RR recombination uncovers a non-germinal center imprint and c-MYC-dependent IGH rearrangement in unmutated chronic lymphocytic leukemia

Cited by 2 publications

References 52 publications

Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era

Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era

Sµ-3’RRrecHigh Chronic Lymphocytic Leukemia is associated with specific gene expression signature, activation-induced cMYC expression and sustained cell cycle entry.

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