Single cell analysis revealed a coexistence of <i><scp>NOTCH</scp>1</i> and <i><scp>TP</scp>53</i> mutations within the same cancer cells in chronic lymphocytic leukaemia patients

Kantorová, Barbara; Malčíková, Jitka; Brázdilová, Kamila; Borský, Marek; Plevová, Karla; Šmardová, Jana; Radová, Lenka; Tom, Nikola; Trbušek, Martin; Divíšková, Eva; Francová, Hana; Navrkalová, Veronika; Doubek, Michael; Brychtová, Yvona; Mayer, Jiřı́; Pospı́šilová, Šárka

doi:10.1111/bjh.14176

Cited by 4 publications

(5 citation statements)

References 10 publications

(12 reference statements)

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“…In particular, a significant correlation between NOTCH1 M and higher CD49d or CD38 expressions was observed, as well a trend towards an association between NOTCH1 M and IGHV UM status, in keeping with previous observations by us and others. 27 , 21 , 4 , 28 Further, co-occurrence of NOTCH1 M and TP53 M characterized 13% of our patients (23 of 178), a rather high percentage if compared to previous reports where concomitant NOTCH1 M and TP53 M, preferentially affecting the same leukemic cells, 29 accounted for 1.2-2.6% of CLL patients. 20 , 23 This may be due to the high number of pre-treated patients and to the low cut-off chosen by us for NOTCH1 M detection.…”

Section: Discussioncontrasting

confidence: 49%

Impaired nodal shrinkage and apoptosis define the independent adverse outcome of NOTCH1 mutated patients under ibrutinib therapy in chronic lymphocytic leukaemia

et al. 2020

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Section: Discussioncontrasting

confidence: 49%

Impaired nodal shrinkage and apoptosis define the independent adverse outcome of NOTCH1 mutated patients under ibrutinib therapy in chronic lymphocytic leukaemia

et al. 2020

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“…Evidence indicates that NOTCH1 mutations can occur in the context of other genetic variables. The concurrent presence of NOTCH1 and TP53 mutations has been described in 1.2–2.6% of CLL patients ( 12 , 21 ), and single cell analysis revealed that gene defects preferentially affected the same leukemic cells ( 61 ). Additional studies observed a high co-occurrence of mutations in MGA, BCOR ( 32 ), and XPO1 genes ( 62 ) with those in NOTCH1 .…”

Section: Notch1 Mutational Status In Cllmentioning

confidence: 99%

NOTCH1 Aberrations in Chronic Lymphocytic Leukemia

et al. 2018

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Chronic lymphocytic leukemia (CLL) is an incurable B-cell neoplasm characterized by highly variable clinical outcomes. In recent years, genomic and molecular studies revealed a remarkable heterogeneity in CLL, which mirrored the clinical diversity of this disease. These studies profoundly enhanced our understanding of leukemia cell biology and led to the identification of new biomarkers with potential prognostic and therapeutic significance. Accumulating evidence indicates a key role of deregulated NOTCH1 signaling and NOTCH1 mutations in CLL. This review highlights recent discoveries that improve our understanding of the pathophysiological NOTCH1 signaling in CLL and the clinical impact of NOTCH1 mutations in retrospective and prospective trials. In addition, we discuss the rationale for a therapeutic strategy aiming at inhibiting NOTCH1 signaling in CLL, along with an overview on the currently available NOTCH1-directed approaches.

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“…In addition, NOTCH1 mutations can also happen with other gene mutations. The coexisting mutations of NOTCH1 and TP53 have been found in about 2.6% of CLL patients, which usually affects the same tumor cells 165 . However, NOTCH1 mutations rarely occur with mutations in the MYD88, SF3B1, and BIRC3 genes 166 .…”

Section: The Role Of the Notch1 Signaling Pathway In Various Types Of...mentioning

confidence: 99%

“…The coexisting mutations of NOTCH1 and TP53 have been found in about 2.6% of CLL patients, which usually affects the same tumor cells. 165 However, NOTCH1 mutations rarely occur with mutations in the MYD88, SF3B1, and BIRC3 genes. 166 NOTCH1 was shown to be an independent poor prognostic factor in CLL based on multivariate analysis.…”

Section: Types Of Notch1 Mutationsmentioning

confidence: 99%

The role of SF3B1 and NOTCH1 in the pathogenesis of leukemia

et al. 2022

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The discovery of new genes/pathways improves our knowledge of cancer pathogenesis and presents novel potential therapeutic options. For instance, splicing factor 3b subunit 1 (SF3B1) and NOTCH1 genetic alterations have been identified at a high frequency in hematological malignancies, such as leukemia, and may be related to the prognosis of involved patients because they change the nature of malignancies in different ways like mediating therapeutic resistance; therefore, studying these gene/pathways is essential. This review aims to discuss SF3B1 and NOTCH1 roles in the pathogenesis of various types of leukemia and the therapeutic potential of targeting these genes or their mutations to provide a foundation for leukemia treatment.

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Single cell analysis revealed a coexistence of NOTCH1 and TP53 mutations within the same cancer cells in chronic lymphocytic leukaemia patients

Cited by 4 publications

References 10 publications

Impaired nodal shrinkage and apoptosis define the independent adverse outcome of NOTCH1 mutated patients under ibrutinib therapy in chronic lymphocytic leukaemia

Impaired nodal shrinkage and apoptosis define the independent adverse outcome of NOTCH1 mutated patients under ibrutinib therapy in chronic lymphocytic leukaemia

NOTCH1 Aberrations in Chronic Lymphocytic Leukemia

The role of SF3B1 and NOTCH1 in the pathogenesis of leukemia

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