Molecular pathogenesis and targeted therapies for NOTCH1-induced T-cell acute lymphoblastic leukemia

Paganin, Maddalena; Ferrando, Adolfo A.

doi:10.1016/j.blre.2010.09.004

Cited by 133 publications

(134 citation statements)

References 133 publications

(175 reference statements)

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“…NOTCH1 mutations in CLL interfere with the C-terminal PEST domain of the protein, which takes part in the proteasomal degradation of the activated form of NOTCH1 [44]. In fact, short PEST domain results in stabilization of the active form of NOTCH1, the molecule impaired degradation, and thus upregulated NOTCH1 signaling [46,47].…”

Section: Notch1mentioning

confidence: 99%

Novel prognostic molecular factors: a quantum leap in the field of chronic lymphocytic leukemia

Zakrzewska

Piróg

Purkot

et al. 2017

Folia Histochem Cytobiol.

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Cytogenetic lesions do not completely explain clinical heterogeneity of chronic lymphocytic leukemia (CLL). The 2016 revision of the World Health Organization classification 2008 indicated that molecular lesions of TP53, NOTCH1, SF3B1 and BIRC3 have potential clinical relevance and could be integrated into an updated risk profile. The negative clinical implications of TP53 disruptions are well constituted and patients with these mutations should be considered for novel, small molecule signal transduction inhibitors therapies. Mutations of NOTCH1, SF3B1 and BIRC3 are associated with poor prognosis. Patients with mutated SF3B1 or NOTCH1 genes present shorter time to first treatment compared to unmutated group. NOTCH1 mutations are related to a high risk of Richter's syndrome transformation, especially in case of TP53 disruptions' coexistence. Large studies on MYD88 mutations in CLL have not explained clearly their clinical importance. The aim of this paper is to provide a comprehensive review on novel molecular aberrations identified in CLL.

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Section: Notch1mentioning

confidence: 99%

Novel prognostic molecular factors: a quantum leap in the field of chronic lymphocytic leukemia

Zakrzewska

Piróg

Purkot

et al. 2017

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] For example, while NOTCH1 mutations are the most common oncogenic lesions in T-ALL, many T-ALLs lacks these or other mutations that activate NOTCH signals. 1,3,4 Combinations of cytotoxic and genotoxic chemotherapeutic drugs that damage organelles and DNA and thus kill proliferating cells are used to treat T-ALL. 2,5,6 Although most T-ALLs are curable, more effective T-ALL therapies are needed since drugresistant and relapsed T-ALLs are significant causes of human cancer morbidity and mortality.…”

Section: Introductionmentioning

confidence: 99%

“…2,5,7 Oncogenic lesions arising in immature T cells cause pediatric T-ALL. [1][2][3] T cells mature via an intra-thymic differentiation program that links assembly and expression of T cell receptor (TCR) genes with cellular survival, proliferation, and continued differentiation. 9 Bone marrow progenitors seed the thymus and differentiate into CD4 ¡ CD8 ¡ (DN) thymocytes, which develop into DN2 thymocytes that proliferate and differentiate into non-proliferating DN3 cells.…”

Section: Introductionmentioning

confidence: 99%

“…10 Genetic changes that block development, prevent apoptosis, and drive proliferation of immature T cells cause pediatric T-ALL. [1][2][3] While all childhood T-ALLs contain mutations that activate oncogenes or inactivate tumor suppressor genes, half of these cancers harbor genomic instability including TCR translocations that target and activate expression of oncogenes.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Somatic inactivation of ATM in hematopoietic cells predisposes mice to cyclin D3 dependent T cell acute lymphoblastic leukemia

et al. 2015

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Overview of non‐coding mutations in chronic lymphocytic leukemia

Spina

Rossi

2019

Molecular Oncology

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Chronic lymphocytic leukemia (CLL) is the most frequent leukemia type in which the genetic alterations influencing the clinico‐biological course are not entirely understood. CLL has a heterogeneous course, with some patients showing an indolent course and others experiencing an aggressive course. Whole‐genome sequencing and whole‐exome sequencing studies identified recurrently mutated genes in CLL and profiled its clonal evolution patterns. However, more recent whole‐genome sequencing studies also identified variants in non‐coding sequences of the CLL genome, revealing important lesions outside the protein‐coding regions. Here we describe the most representative non‐coding lesion of the CLL genome, including lesions in the 3′‐UTR region of NOTCH1 which result in the truncation of the NOTCH1 protein PEST domain, and non‐coding mutations in an enhancer region on chromosome 9p13 which result in reduced expression of the PAX5 transcription factor. In addition, we describe the role of microRNA in CLL, in particular the miR15a/miR16‐1 microRNA recurrently affected by deletions of chromosome 13q14. Together, new findings in non‐coding genome genetic lesions provide a more complete portrait of the genomic landscape of CLL with clinical implications.

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Molecular pathogenesis and targeted therapies for NOTCH1-induced T-cell acute lymphoblastic leukemia

Cited by 133 publications

References 133 publications

Novel prognostic molecular factors: a quantum leap in the field of chronic lymphocytic leukemia

Novel prognostic molecular factors: a quantum leap in the field of chronic lymphocytic leukemia

Somatic inactivation of ATM in hematopoietic cells predisposes mice to cyclin D3 dependent T cell acute lymphoblastic leukemia

Overview of non‐coding mutations in chronic lymphocytic leukemia

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