<i>TET2</i> and <i>TP53</i> mutations are frequently observed in blastic plasmacytoid dendritic cell neoplasm

Jardin, Fabrice; Ruminy, Philippe; Parmentier, Françoise; Troussard, Xavier; Vaida, Iona; Stamatoullas, Aspasia; Leprêtre, Stéphane; Penther, Dominique; Duval, A B; Picquenot, Jean‐Michel; Courville, Philippe; Capiod, Jean‐Claude; Tilly, Hervé; Bastard, Christian; Marolleau, Jean Pierre

doi:10.1111/j.1365-2141.2010.08556.x

Cited by 82 publications

(77 citation statements)

References 10 publications

(12 reference statements)

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“…26 However, the occurrence of this mutation in BPCDN is debated; Jardin et al did not find the mutation in any of 15 BPCDN cases, while a previous study showed that FLT3-ITD could also be expressed by dendritic cells. 27,28 At present no other clinical studies have supported our observation, but this is probably because the FLT3-ITD mutation was not searched for in large numbers of cases of BPDCN. If our finding is confirmed, it would indicate that FLT3 inhibitors could be a potential therapy for these patients.…”

Section: Discussionmentioning

confidence: 74%

“…The available studies are retrospective and different treatments were used: the majority of patients received multi-agent chemotherapy, according to ALL or AML schedules, while a few cases underwent allogeneic HSCT. 9,22,[27][28][29][30][31][32][33][34] The response rates and survival of the patients in the main previous studies are summarized in Table 4, in which we report the largest published series on adult and pediatric populations with at least five cases of BPDCN. 9,16,22,[29][30][31] It emerges that BPDCN is quite sensitive to chemotherapy initially, with complete response rates ranging from 53% to 89%.…”

Section: Discussionmentioning

confidence: 99%

“…The only available data published in detail derive from small series of patients or single case reports, most showing that intensive therapy for acute leukemia increased the rate of complete remissions, but only myeloablative treatment with allogeneic HSCT during the first remission resulted in the chance of a significant improvement in overall survival, especially in younger patients. 22,27,29,[31][32][33][34] In the French analysis by Dalle et al, among 47 patients with BPDCN, ten were transplanted during the management of their disease (9 allogeneic transplants, 1 autologous transplant; median age 38 years); the transplanted patients had a significantly longer survival (31.3 months) than that of the non-transplanted patients (median of only 12 months). 29 Moreover, Dietrich et al described four patients who underwent allogeneic HSCT, of whom two were allografted in remission and were alive and disease-free at 57 and 16 month posttransplant.…”

Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 99%

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Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: an Italian multicenter study

Pagano

Valentini

Pulsoni³

et al. 2012

Haematologica

276

365

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The objective of this study was to evaluate the clinical features, prognostic factors, and efficacy of treatments in patients with blastic plasmacytoid dendritic cell neoplasm with a leukemic presentation at onset of the disease. In order to do this, a retrospective multicenter study was performed from 2005-2011 in 28 Italian hematology divisions in which 43 cases were collected. Forty-one patients received an induction therapy, consisting of an acute myeloid leukemia-type regimen in 26 patients (60%) and acute lymphoid leukemia/lymphoma-type regimen in 15 patients (35%). Six patients (14%) underwent allogeneic hematopoietic stem cell transplantation. Seventeen patients (41%) achieved a complete remission: seven after acute myeloid leukemia-type treatment and 10 after an acute lymphoid leukemia/lymphoma-type regimen, with a significant advantage for acute lymphoid leukemia/lymphoma-type chemotherapy (P=0.02). Relapse occurred in six of the 17 patients (35%) who achieved complete remission, more frequently after acute lymphoid leukemia/lymphoma-type chemotherapy. The median overall survival was 8.7 months (range, 0.2-32.9). The patients treated with an acute myeloid leukemia-type regimen had an overall survival of 7.1 months (range, 0.2-19.5), whereas that of the patients receiving acute lymphoid leukemia/lymphoma-type chemotherapy was 12.3 months (range, 1-32.9) (P=0.02). The median overall survival of the allogeneic hematopoietic stem cell transplant recipients was 22.7 months (range, 12-32.9), and these patients had a significant survival advantage compared to the non-transplanted patients (median 7.1 months, 0.2-21.3; P=0.03). In conclusion, blastic plasmacytoid dendritic cell neoplasm with bone-marrow involvement is an aggressive subtype of high-risk acute leukemia. The rarity of this disease does not enable prospective clinical trials to identify the better therapeutic strategy, which, at present, is based on clinicians' experience. Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: an Italian multicenter study

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 99%

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Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: an Italian multicenter study

Pagano

Valentini

Pulsoni³

et al. 2012

Haematologica

276

365

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“…8,9 BPDCN presents heterogeneous genetic features characterized by chromosomal losses and deletions 10,11 and a mutational landscape that overlaps with other hematologic malignancies without evidence of unique, disease-specific, driver genetic lesions. [12][13][14] As in myeloid and lymphoid malignancies, mutations in key epigenetic modifierencoding genes, such as TET2, ASXL1, and EZH2, have been described in a proportion of BPDCN cases, thus supporting a role for deregulation of epigenetic signaling in disease pathogenesis. [12][13][14] Gene expression profiling (GEP), although performed in relatively few cases, has shown a distinctive transcriptional program in BPDCN characterized by predominant expression of genes that are typical of the pDC lineage 15,16 and evidence of aberrant activation of the NF-kB pathway.…”

Section: Introductionmentioning

confidence: 99%

Haploinsufficiency for NR3C1, the gene encoding the glucocorticoid receptor, in blastic plasmacytoid dendritic cell neoplasms

Emadali

Hoghoughi

Duley

et al. 2016

Blood

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Key Points• NR3C1 haploinsufficiency is found in patients with a plasmacytoid dendritic cell neoplasm characterized by very poor clinical outcome.• Overexpression of lincRNA3q is a consistent feature of malignant cells in these patients and can be abrogated by BET protein inhibition.Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive leukemia for which knowledge on disease mechanisms and effective therapies are currently lacking. Only a handful of recurring genetic mutations have been identified and none is specific to BPDCN. In this study, through molecular cloning in an index case that presented a balanced t(3;5)(q21;q31) and molecular cytogenetic analyses in a further 46 cases, we identify monoallelic deletion of NR3C1 (5q31), encoding the glucocorticoid receptor (GCR), in 13 of 47 (28%) BPDCN patients. Targeted deep sequencing in 36 BPDCN cases, including 10 with NR3C1 deletion, did not reveal NR3C1 point mutations or indels. Haploinsufficiency for NR3C1 defined a subset of BPDCN with lowered GCR expression and extremely poor overall survival (P 5 .0006). Consistent with a role for GCR in tumor suppression, functional analyses coupled with gene expression profiling identified corticoresistance and loss-of-EZH2 function as major downstream consequences of NR3C1 deletion in BPDCN. Subsequently, more detailed analyses of the t(3;5)(q21;q31) revealed fusion of NR3C1 to a long noncoding RNA (lncRNA) gene (lincRNA-3q) that encodes a novel, nuclear, noncoding RNA involved in the regulation of leukemia stem cell programs and G1/S transition, via E2F. Overexpression of lincRNA-3q was a consistent feature of malignant cells and could be abrogated by bromodomain and extraterminal domain (BET) protein inhibition. Taken together, this work points to NR3C1 as a haploinsufficient tumor suppressor in a subset of BPDCN and identifies BET inhibition, acting at least partially via lncRNA blockade, as a novel treatment option in BPDCN. (Blood. 2016;127(24):3040-3053)

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“…Sanger sequencing study (n=13) described TET2 gene mutations in 53% (7/13) 6 . Whole exome sequencing (n=3) revealed multiple protein-coding changes but no common mutation, which underlines the genetic diversity within the condition (Table 1) 7…”

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confidence: 99%

Clonal evolution in the transition from cutaneous disease to acute leukemia suggested by liquid biopsy in blastic plasmacytoid dendritic cell neoplasm

et al. 2018

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TET2 and TP53 mutations are frequently observed in blastic plasmacytoid dendritic cell neoplasm

Cited by 82 publications

References 10 publications

Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: an Italian multicenter study

Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: an Italian multicenter study

Haploinsufficiency for NR3C1, the gene encoding the glucocorticoid receptor, in blastic plasmacytoid dendritic cell neoplasms

Clonal evolution in the transition from cutaneous disease to acute leukemia suggested by liquid biopsy in blastic plasmacytoid dendritic cell neoplasm

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