Comparison of TP53 mutations screening by functional assay of separated allele in yeast and next-generation sequencing in myelodysplastic syndromes

Bally, Cécile; Renneville, Aline; Preudhomme, Claude; Legrand, Martine; Adès, Lionel; Fenaux, Pierre; Lehmann-Che, Jacqueline

doi:10.1016/j.leukres.2015.07.001

Cited by 2 publications

(2 citation statements)

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“…Data obtained from these analyses revealed that mutations of p53 that retain some transcriptional activity are associated with a milder family history of cancer development, a lower number of tumors and a delayed disease onset [ 34 ]. Owing to the growing place taken by p53 in cancer research, FASAY has been used to determine the p53 status of various human tumors such as leukemia [ 35 ], hepatocellular carcinoma [ 36 ] and myelodysplastic syndromes [ 37 ] (see [ 38 ] for review). FASAY also allowed to determine the dominant-negative potential of p53 mutations in various tumors [ 30 , 31 , 39 ] and helped characterizing the p53 status of various cancer cell lines [ 14 ].…”

Section: Fasay In Diagnosismentioning

confidence: 99%

“…FASAY appears even better suited than immunohistochemistry. Indeed, immunochemistry relies on the excessive accumulation of mutant p53 protein, a phenomenon that is far from being systematic and varies depending on the considered mutation [ 42 ]. However, no current technology is able to identify all p53 alterations in cancers and FASAY does not permit the identification of the incriminated mutation.…”

Section: Fasay In Diagnosismentioning

confidence: 99%

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p53, p63 and p73 in the wonderland ofS. cerevisiae

Blondel

Voisset

2017

Oncotarget

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Since its discovery in 1979, p53 has been on the forefront of cancer research. It is considered a master gene of cancer suppression and is found mutated in around 50% of all human tumors. In addition, the progressive identification of p53-related transcription factors p63 and p73 as well as their multiple isoforms have added further layers of complexity to an already dense network. Among the numerous models used to unravel the p53 family mysteries, S. cerevisiae has been particularly useful. This seemingly naive model allows the expression of a functional human p53 and thus the assessment of p53 intrinsic transcriptional activity. The aim of this article is to review the various contributions that the budding yeast has made to the understanding of p53, p63 and p73 biology and to envision new possible directions for yeast-based assays in the field of cancer as well as other p53-family-related diseases.

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Section: Fasay In Diagnosismentioning

confidence: 99%

Section: Fasay In Diagnosismentioning

confidence: 99%

p53, p63 and p73 in the wonderland ofS. cerevisiae

Blondel

Voisset

2017

Oncotarget

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Treatment of Lymphoid and Myeloid Malignancies by Immunomodulatory Drugs

Fuchs

2019

CHDDT

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Thalidomide and its derivatives (lenalidomide, pomalidomide, avadomide, iberdomide hydrochoride, CC-885 and CC-90009) form the family of immunomodulatory drugs (IMiDs). Lenalidomide (CC5013, Revlimid®) was approved by the US FDA and the EMA for the treatment of multiple myeloma (MM) patients, low or intermediate-1 risk transfusion-dependent myelodysplastic syndrome (MDS) with chromosome 5q deletion [del(5q)] and relapsed and/or refractory mantle cell lymphoma following bortezomib. Lenalidomide has also been studied in clinical trials and has shown promising activity in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Lenalidomide has anti-inflammatory effects and inhibits angiogenesis. Pomalidomide (CC4047, Imnovid® [EU], Pomalyst® [USA]) was approved for advanced MM insensitive to bortezomib and lenalidomide. Other IMiDs are in phases 1 and 2 of clinical trials. Cereblon (CRBN) seems to have an important role in IMiDs action in both lymphoid and myeloid hematological malignancies. Cereblon acts as the substrate receptor of a cullin-4 really interesting new gene (RING) E3 ubiquitin ligase CRL4CRBN. This E3 ubiquitin ligase in the absence of lenalidomide ubiquitinates CRBN itself and the other components of CRL4CRBN complex. Presence of lenalidomide changes specificity of CRL4CRBN which ubiquitinates two transcription factors, IKZF1 (Ikaros) and IKZF3 (Aiolos), and casein kinase 1α (CK1α) and marks them for degradation in proteasomes. Both these transcription factors (IKZF1 and IKZF3) stimulate proliferation of MM cells and inhibit T cells. Low CRBN level was connected with insensitivity of MM cells to lenalidomide. Lenalidomide decreases expression of protein argonaute-2, which binds to cereblon. Argonaute-2 seems to be an important drug target against IMiDs resistance in MM cells. Lenalidomide decreases also basigin and monocarboxylate transporter 1 in MM cells. MM cells with low expression of Ikaros, Aiolos and basigin are more sensitive to lenalidomide treatment. The CK1α gene (CSNK1A1) is located on 5q32 in commonly deleted region (CDR) in del(5q) MDS. Inhibition of CK1α sensitizes del(5q) MDS cells to lenalidomide. CK1α mediates also survival of malignant plasma cells in MM. Though, inhibition of CK1α is a potential novel therapy not only in del(5q) MDS but also in MM. High level of full length CRBN mRNA in mononuclear cells of bone marrow and of peripheral blood seems to be necessary for successful therapy of del(5q) MDS with lenalidomide. While transfusion independence (TI) after lenalidomide treatment is more than 60% in MDS patients with del(5q), only 25% TI and substantially shorter duration of response with occurrence of neutropenia and thrombocytopenia were achieved in lower risk MDS patients with normal karyotype treated with lenalidomide. Shortage of the biomarkers for lenalidomide response in these MDS patients is the main problem up to now.

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Comparison of TP53 mutations screening by functional assay of separated allele in yeast and next-generation sequencing in myelodysplastic syndromes

Cited by 2 publications

References 32 publications

p53, p63 and p73 in the wonderland ofS. cerevisiae

p53, p63 and p73 in the wonderland ofS. cerevisiae

Treatment of Lymphoid and Myeloid Malignancies by Immunomodulatory Drugs

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