Proliferation centers in chronic lymphocytic leukemia: the niche where NF-κB activation takes place

Herreros, Beatriz; Rodríguez‐Pinilla, Socorro María; Pajares, Raquel; Martínez-González, M Á; Ramos, Rafael; Muñoz, Inés G.; Montes‐Moreno, Santiago; Lozano, Miquel; Sánchez-Verde, Lydia; Roncador, Giovanna; Sánchez‐Beato, Margarita; Otazu, R. Díaz de; Pérez‐Guillermo, Miguel; Mestre, María J.; Bellas, Carmen; Piris, Miguel Á.

doi:10.1038/leu.2009.285

Cited by 33 publications

(22 citation statements)

References 16 publications

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“…However, surface CXCR4 was downregulated in LNS1 cocultures (supplemental Figure 2G-H). This finding is consistent with the observations that compared with Hs5 cells, LNS1 cells express high levels of CXCL12 (supplemental Figure 2I), as previously reported for stromal cells in CLL lymph nodes, 39 and surface CXCR4 is downregulated via receptor endocytosis in CLL cells in the presence of high CXCL12. For personal use only.…”

Section: Hif-1a Is Transcriptionally Regulated In Cll Cells Upon Cocusupporting

confidence: 93%

HIF-1α regulates the interaction of chronic lymphocytic leukemia cells with the tumor microenvironment

Valsecchi

Coltella

Belloni

et al. 2016

Blood

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Section: Hif-1a Is Transcriptionally Regulated In Cll Cells Upon Cocusupporting

confidence: 93%

HIF-1α regulates the interaction of chronic lymphocytic leukemia cells with the tumor microenvironment

Valsecchi

Coltella

Belloni

et al. 2016

Blood

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“…This kind of mutation should give rise to a truncated protein without the ankyrin motif mediating the protein–protein interaction and would eventually be degraded. The inactivation of NFKBIE by mutation would lead to the sustained activation of the NFKB pathway (Figure S2), which has previously been linked to CLL pathogenesis [20] …”

Section: Discussionmentioning

confidence: 99%

New Mutations in Chronic Lymphocytic Leukemia Identified by Target Enrichment and Deep Sequencing

et al. 2012

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Chronic lymphocytic leukemia (CLL) is a heterogeneous disease without a well-defined genetic alteration responsible for the onset of the disease. Several lines of evidence coincide in identifying stimulatory and growth signals delivered by B-cell receptor (BCR), and co-receptors together with NFkB pathway, as being the driving force in B-cell survival in CLL. However, the molecular mechanism responsible for this activation has not been identified. Based on the hypothesis that BCR activation may depend on somatic mutations of the BCR and related pathways we have performed a complete mutational screening of 301 selected genes associated with BCR signaling and related pathways using massive parallel sequencing technology in 10 CLL cases. Four mutated genes in coding regions (KRAS, SMARCA2, NFKBIE and PRKD3) have been confirmed by capillary sequencing. In conclusion, this study identifies new genes mutated in CLL, all of them in cases with progressive disease, and demonstrates that next-generation sequencing technologies applied to selected genes or pathways of interest are powerful tools for identifying novel mutational changes.

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“…1,7 However, the complexity of the microenvironment of proliferation centers has not been completely elucidated. 32 In addition, the clinical significance of the number and size of proliferation centers, where proliferation of CLL takes place, remains to be established. Historically, Lennert 10,31 recognized a histological "tumor-forming" type of CLL characterized by an excessive prolymphocyte proliferation, resulting in large lighter regions when examined under the microscope.…”

Section: Discussionmentioning

confidence: 99%

Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia ("accelerated" chronic lymphocytic leukemia) with aggressive clinical behavior

Giné

Martı́nez²,

Villamor³

et al. 2010

Haematologica

167

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BackgroundThe concept of "accelerated" chronic lymphocytic leukemia is frequently used by both pathologists and clinicians. However, neither histological criteria to define this form of chronic lymphocytic leukemia nor its clinical correlates and prognostic impact have been formally defined in large series of patients. Design and MethodsTissue biopsies from 100 patients with chronic lymphocytic leukemia were analyzed for the size of proliferation centers and their proliferation rate as assessed by mitosis count and Ki-67 immunostaining. Histological patterns were correlated with main clinico-biological features and outcome. ResultsA suspicion of disease transformation was the main reason for carrying out tissue biopsy, which was performed at a median time of 14 months (range, 0 to 204 months) after the diagnosis of chronic lymphocytic leukemia. The biopsy showed histological transformation to diffuse large B-cell lymphoma in 22 cases. In the remaining 78 patients, the presence of expanded proliferation centers (broader than a 20x field) and high proliferation rate (either >2.4 mitoses/proliferation center or Ki-67 >40%/proliferation center) predicted a poor outcome and were selected to define a highly proliferative group. Thus, 23 patients with either expanded proliferation centers or high proliferation rate were considered as having "accelerated" chronic lymphocytic leukemia. These patients displayed particular features, including higher serum lactate dehydrogenase levels and more frequently elevated ZAP-70 than "non-accelerated" cases. The median survival from biopsy of patients with "non-accelerated" chronic lymphocytic leukemia, "accelerated" chronic lymphocytic leukemia and transformation to diffuse large Bcell leukemia was 76, 34, and 4.3 months, respectively (P<0.001). ConclusionsThe presence of expanded and/or highly active proliferation centers identifies a group of patients with "accelerated" chronic lymphocytic leukemia characterized by an aggressive clinical behavior.Key words: accelerated chronic lymphocytic leukemia, lymph node biopsy, ZAP-70. Haematologica 2010;95(9):1526-1533. doi:10.3324/haematol.2010 This is an open-access paper. Citation: Giné E, MartinezExpanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia ("accelerated" chronic lymphocytic leukemia) with aggressive clinical behavior

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Proliferation centers in chronic lymphocytic leukemia: the niche where NF-κB activation takes place

Cited by 33 publications

References 16 publications

HIF-1α regulates the interaction of chronic lymphocytic leukemia cells with the tumor microenvironment

HIF-1α regulates the interaction of chronic lymphocytic leukemia cells with the tumor microenvironment

New Mutations in Chronic Lymphocytic Leukemia Identified by Target Enrichment and Deep Sequencing

Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia ("accelerated" chronic lymphocytic leukemia) with aggressive clinical behavior

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