Chronic lymphocytic leukemia–like monoclonal B-cell lymphocytosis exhibits an increased inflammatory signature that is reduced in early-stage chronic lymphocytic leukemia

Blanco, Gonzalo; Puiggros, Anna; Sherry, Barbara; Nonell, Lara; Calvo, Xavier; Puigdecanet, Eulàlia; Chiu, Pui Yan; Kieso, Yasmine; Ferrer, Gerardo; Palacios, Florencia; Arnal, Magdalena; Rodríguez‐Rivera, Maria; Gimeno, Eva; Abella, Eugènia; Kanti, R.; Bosch, Francesc; Calon, Alexandre; Ferrer, Ana; Chiorazzi, Nicholas; Espinet, Blanca

doi:10.1016/j.exphem.2020.12.007

Cited by 8 publications

(8 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, frequencies of both the M1 and M2 populations were elevated in blood of B-CLL patients versus control individuals ( 57 ). Recently, a clinical study found that an inflammatory blood monocyte profile was strongly associated with the B-CLL precursor state, MBL, but less apparent as patients progressed to frank B-CLL ( 124 ). Thus, the proportion of these subpopulations may change as leukemia progresses.…”

Section: Discussionmentioning

confidence: 99%

B Cell Chronic Lymphocytic Leukemia Development in Mice with Chronic Lung Exposure toCoccidioidesFungal Arthroconidia

et al. 2023

View full text Add to dashboard Cite

Links between repeated microbial infections and B cell chronic lymphocytic leukemia (B-CLL) have been proposed but not tested directly. This study examines how prolonged exposure to a human fungal pathogen impacts B-CLL development in Eµ-hTCL1–transgenic mice. Monthly lung exposure to inactivated Coccidioides arthroconidia, agents of Valley fever, altered leukemia development in a species-specific manner, with Coccidioides posadasii hastening B-CLL diagnosis/progression in a fraction of mice and Coccidioides immitis delaying aggressive B-CLL development, despite fostering more rapid monoclonal B cell lymphocytosis. Overall survival did not differ significantly between control and C. posadasii–treated cohorts but was significantly extended in C. immitis–exposed mice. In vivo doubling time analyses of pooled B-CLL showed no difference in growth rates of early and late leukemias. However, within C. immitis–treated mice, B-CLL manifests longer doubling times, as compared with B-CLL in control or C. posadasii–treated mice, and/or evidence of clonal contraction over time. Through linear regression, positive relationships were noted between circulating levels of CD5+/B220low B cells and hematopoietic cells previously linked to B-CLL growth, albeit in a cohort-specific manner. Neutrophils were positively linked to accelerated growth in mice exposed to either Coccidioides species, but not in control mice. Conversely, only C. posadasii–exposed and control cohorts displayed positive links between CD5+/B220low B cell frequency and abundance of M2 anti-inflammatory monocytes and T cells. The current study provides evidence that chronic lung exposure to fungal arthroconidia affects B-CLL development in a manner dependent on fungal genotype. Correlative studies suggest that fungal species differences in the modulation of nonleukemic hematopoietic cells are involved.

show abstract

Section: Discussionmentioning

confidence: 99%

B Cell Chronic Lymphocytic Leukemia Development in Mice with Chronic Lung Exposure toCoccidioidesFungal Arthroconidia

et al. 2023

View full text Add to dashboard Cite

show abstract

“…This process is commonly known as cancer immunosurveillance ( 123 ). In relation to the latter, a recent study found differences in the inflammatory signatures between MBL and CLL ( 124 ). Likewise, sustained CLL remissions, particularly with novel therapeutic agents that modulate the immune system, may be contingent upon antitumor immunity, with immune escape presaging disease relapse.…”

Section: The Molecular Basis Of Cll Intratumoral Heterogeneity and Evolutionmentioning

confidence: 99%

Clonal Evolution of High-Risk Chronic Lymphocytic Leukemia: A Contemporary Perspective

Kwok

2021

Front. Oncol.

View full text Add to dashboard Cite

Clonal evolution represents the natural process through which cancer cells continuously search for phenotypic advantages that enable them to develop and expand within microenvironmental constraints. In chronic lymphocytic leukemia (CLL), clonal evolution underpins leukemic progression and therapeutic resistance, with differences in clonal evolutionary dynamics accounting for its characteristically diverse clinical course. The past few years have witnessed profound changes in our understanding of CLL clonal evolution, facilitated by a maturing definition of high-risk CLL and an increasing sophistication of next-generation sequencing technology. In this review, we offer a modern perspective on clonal evolution of high-risk CLL, highlighting recent discoveries, paradigm shifts and unresolved questions. We appraise recent advances in our understanding of the molecular basis of CLL clonal evolution, focusing on the genetic and non-genetic sources of intratumoral heterogeneity, as well as tumor-immune dynamics. We review the technological innovations, particularly in single-cell technology, which have fostered these advances and represent essential tools for future discoveries. In addition, we discuss clonal evolution within several contexts of particular relevance to contemporary clinical practice, including the settings of therapeutic resistance to CLL targeted therapy and immunotherapy, as well as Richter transformation of CLL to high-grade lymphoma.

show abstract

“…On certain occasions, tumor regression associates with external factors such as infections, blood transfusions, or the emergence of secondary malignancies, potentially reflecting the induction of a proinflammatory immune environment [12,13]. In this context, we recently described an increased inflammatory signature in patients with the pre-leukemic stage of CLL, referred to as monoclonal B-cell lymphocytosis (MBL) [14]. Both CLL SR and MBL could be viewed as scenarios in which the proliferation of CLL cells is somehow controlled or even reduced.…”

Section: Introductionmentioning

confidence: 99%

Spontaneous Regression Accompanied by Concomitant Immune Alterations in a Patient with Chronic Lymphocytic Leukemia

2024

Ann Case Report

View full text Add to dashboard Cite

Spontaneous regression (SR) of chronic lymphocytic leukemia (CLL) is a rare event (0.2% -1%). Some advances have been made in understanding the tumor genetic characteristics of such patients, although the immunological mechanisms leading to SR remain unclear. We describe a series of immunological events related to regression dynamics, allowing the identification of a SR phase (associated with >99% reduction of CLL cells in peripheral blood and adenopathy resolution in less than one year, concurrently with a nine-fold increase in monocyte counts, high B2M and the appearance of an oligoclonal serum IgG band), followed by a persistent regression (PR) phase that was maintained for ≥17 months. Our observations highlight a role of monocytes and B2M in SR, potentially related to immune activation. The oligoclonal IgG band detected during SR was maintained in PR, suggesting either a change in the ability of malignant cells (IgM + IgD + IgG -) to differentiate into IgG-secreting cells, or an anti-tumor humoral response from normal B cells. These findings imply immune and molecular mechanisms required to eliminate malignant cells and might suggest new immunotherapies for CLL.

show abstract

Chronic lymphocytic leukemia–like monoclonal B-cell lymphocytosis exhibits an increased inflammatory signature that is reduced in early-stage chronic lymphocytic leukemia

Cited by 8 publications

References 56 publications

B Cell Chronic Lymphocytic Leukemia Development in Mice with Chronic Lung Exposure toCoccidioidesFungal Arthroconidia

B Cell Chronic Lymphocytic Leukemia Development in Mice with Chronic Lung Exposure toCoccidioidesFungal Arthroconidia

Clonal Evolution of High-Risk Chronic Lymphocytic Leukemia: A Contemporary Perspective

Spontaneous Regression Accompanied by Concomitant Immune Alterations in a Patient with Chronic Lymphocytic Leukemia

Contact Info

Product

Resources

About