The Krüppel-like factor 2 transcription factor gene is recurrently mutated in splenic marginal zone lymphoma

Piva, Roberto; Deaglio, Silvia; Famà, Rosella; Buonincontri, Roberta; Scarfò, Irene; Bruscaggin, Alessio; Mereu, Elisabetta; Serra, Sara; Spina, Valeria; Brusa, Davide; Garaffo, Giulia; Monti, Sara; Bo, Michele Dal; Marasca, Roberto; Arcaini, Luca; Neri, Antonino; Gattei, Valter; Paulli, Marco; Tiacci, Enrico; Bertoni, Francesco; Pileri, Stefano; Foà, Robin; Inghirami, Giorgio; Gaïdano, Gianluca; Rossi, Davide

doi:10.1038/leu.2014.294

Cited by 87 publications

(81 citation statements)

References 14 publications

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“…5 From this panel, the following candidate genes were selected for Sanger validation (primers and conditions are listed in supplemental Table 1) based on the high prevalence of somatic mutations in similar mature B-cell malignancies: KLF2 and NOTCH2 (splenic marginal zone lymphoma [SMZL]), [5][6][7][8][9] CCND3 and BCOR (splenic diffuse red pulp lymphoma [SDRPL]), 10,11 MAP2K1 (hairy cell variant [HCL-v]), 12 MYD88 (lymphoplasmacytic lymphoma [LPL]), 13 BRAF V600E (hairy cell leukemia and nodal marginal zone lymphoma [MZL]), 14,15 and TNFAIP3 and TP53 (not disease specific). DNA from buccal cells (n 5 22) was used to confirm the somatic origin of 14 of 15 variants identified in 7 of these genes.…”

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confidence: 99%

CBL-MZ is not a single biological entity: evidence from genomic analysis and prolonged clinical follow-up

et al. 2018

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The term "clonal B cell lymphocytosis of marginal zone origin" (CBL-MZ) 1,2 has recently been suggested for asymptomatic individuals whose routine blood count shows a persistent modest lymphocytosis that is usually accompanied by bone marrow involvement. This immunophenotype is suggestive of marginal zone/postgerminal center derivation, but no other features of a chronic B cell lymphoproliferative disorder are found, other than a low-level paraprotein in some cases. Cases with a clonal lymphocyte count ,5 3 10 9 /L would fall within the revised World Health Organization (WHO) category of non-chronic lymphocytic leukemia-type monoclonal B-cell lymphocytosis. In 3 previous series of CBL-MZ consisting of 102, 53, and 16 cases with median follow-ups (FUs) of 60, 34, and 44 months, respectively, 1,3,4 the overall incidence of progression was 15.7%, with the majority (11.1%) developing splenomegaly that frequently did not require treatment. However, it remains unclear whether CBL-MZ is the precursor to 1 or several well-defined WHO entities and what factors predict disease progression. To address this, we performed a genomic analysis of a well-characterized cohort of CBL-MZ cases with long FU and provide evidence to show that CBL-MZ is not a single biological entity.This study includes data from 37 patients with CBL-MZ diagnosed and managed at the Royal Bournemouth Hospital. Clinical, routine laboratory, morphological, immunophenotypic, immunogenetic, and cytogenetic data have been reported on 36 cases using previously described methods.

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confidence: 99%

CBL-MZ is not a single biological entity: evidence from genomic analysis and prolonged clinical follow-up

et al. 2018

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“…Similar gene panel-based efforts have also been performed for SMZL, revealing a high frequency of TP53, KLF2, NOTCH2, TNFAIP3, and MYD88 mutations, 17,18 and demonstrating NOTCH2 and TP53 mutations as independent markers of short treatment-free and overall survival, respectively. 16 Nonetheless, caution is required given the retrospective nature of the published studies and the overall rarity of SMZL raising concerns about potential selection biases.…”

Section: Genes With Prognostic Potentialmentioning

confidence: 98%

“…52 Moreover, some gene mutations are mainly found in a specific lymphoma entity at a relatively high frequency, whereas they are rare in other subtypes, e.g. ID3 and TCF3 mutations in BL, 19 KLF2 in SMZL, [16][17][18] SF3B1 mutations in CLL, 14,15 RHOA mutations in AITL and other PTCL with a follicular helper T cell (T FH ) phenotype, 13,20,21,[53][54][55][56][57][58][59] and, very recently, the novel somatic mutations in RRAGC encoding a Rag GTPase protein (RagC) that were enriched in FL (16%) but were absent in other mature Bcell lymphomas. 60 That said, a pattern has started to emerge in recent years where certain lymphoma entities 'share' common types of genetic events affecting selected pathways or biological mechanisms ( Figure 1).…”

Section: Genes Of Diagnostic Potentialmentioning

confidence: 99%

“…In addition, while some genes are biased to certain lymphoma entities, e.g. SF3B1 mutations in CLL, 14,15 KLF2 mutations in SMZL, [16][17][18] ID3 and TCF3 mutations in BL, 19 STAT3 mutations in large granular lymphocyte (LGL) leukemia, 11 and RHOA mutations in angioimmunoblastic T-cell lymphoma (AITL), 20,21 other genes found recurrently mutated, such as genes involved in DNA repair, epigenetic modification and regulation of transcription (Figure 1), can be detected in multiple subtypes (Table 1) and even in other cancer types.…”

Section: Clinical Impact Of Recurrently Mutated Genes On Lymphoma Diamentioning

confidence: 99%

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Clinical impact of recurrently mutated genes on lymphoma diagnostics: state-of-the-art and beyond

Rosenquist

Rosenwald

et al. 2016

Haematologica

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“…Additionally, KLF2 mutations were observed in 30% of marginal zone lymphoma (MZL) and diffuse large B‐cell lymphoma cases 29. KLF2 is a transcription factor that controls the differentiation of multiple B‐cell subpopulations, including marginal zone B cells.…”

Section: What Has Recently Improved the Understanding Of Hcl And Hcl‐mentioning

confidence: 99%

Hairy cell leukemia 2018: Update on diagnosis, risk‐stratification, and treatment

Troussard

Cornet

2017

American J Hematol

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Disease overviewHairy cell leukemia (HCL) and HCL‐like disorders, including HCL variant (HCL‐V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B‐cell disorders, characterized by the identification of hairy cells, a specific genetic profile, a different clinical course and the need for appropriate treatment.DiagnosisDiagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11C, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAF V600E somatic mutation.Risk stratificationProgression of patients with HCL is based on a large splenomegaly, leukocytosis, a high number of hairy cells in the peripheral blood and the immunoglobulin heavy chain variable region gene mutational status. VH4‐34 positive HCL cases are associated with poor prognosisRisk adapted therapyPurine analogs (PNA) are indicated in symptomatic first line HCL patients. The use of PNA followed by rituximab represents an alternative option.Management of progressive or refractory diseaseIt is based on the use of BRAF inhibitors associated or not with MEK inhibitors, recombinant immunoconjugates targeting CD22 or BCR inhibitors.

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The Krüppel-like factor 2 transcription factor gene is recurrently mutated in splenic marginal zone lymphoma

Cited by 87 publications

References 14 publications

CBL-MZ is not a single biological entity: evidence from genomic analysis and prolonged clinical follow-up

CBL-MZ is not a single biological entity: evidence from genomic analysis and prolonged clinical follow-up

Clinical impact of recurrently mutated genes on lymphoma diagnostics: state-of-the-art and beyond

Hairy cell leukemia 2018: Update on diagnosis, risk‐stratification, and treatment

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