Elevated
            <i>FANCA</i>
            expression determines a worse prognosis in chronic lymphocytic leukemia and interferes with p53 function

Bravo-Navas, Sara; Yáñez, Lucrecia; Romón, Íñigo; Pipaón, Carlos

doi:10.1096/fj.201802439rr

Cited by 8 publications

(7 citation statements)

References 35 publications

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“…FANCB participates in the E3 complex that monoubiquitinates FANCD2 and FANCI as part of the detection and signaling of DSB, but none of those proteins showed variations in their modifications, maybe suggesting a role of FANCB in CLL aside of the FANCcore complex. In that direction, overexpression of FANCA have been found as a bad prognosis factor in CLL, since it collaborates with MDM2 in the destabilization of p53 ( 34 ). Moreover, FANCA is necessary in the NEDDylation of several CLL markers like CXCR5, beta-2-microglobulin and CD44 ( 35 ).…”

Section: Distribution Of the Ubiquitin-like Modifications In Cllmentioning

confidence: 98%

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A Different View for an Old Disease: NEDDylation and Other Ubiquitin-Like Post-Translational Modifications in Chronic Lymphocytic Leukemia

et al. 2021

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Despite the enormous amount of molecular data obtained over the years, the molecular etiology of chronic lymphocytic leukemia (CLL) is still largely unknown. All that information has enabled the development of new therapeutic approaches that have improved life expectancy of the patients but are still not curative. We must increase our knowledge of the molecular alterations responsible for the characteristics common to all CLL patients. One of such characteristics is the poor correlation between mRNA and protein expression, that suggests a role of post-translational mechanisms in CLL physiopathology. Drugs targeting these processes have indeed demonstrated an effect either alone or in combination with other aimed at specific pathways. A recent article unveiled an increment in ubiquitin-like modifications in CLL, with many protein members of relevant pathways affected. Interestingly, the inhibition of the NEDD8-activating protein NAE reverted a substantial number of those modifications. The present review gets the scarce data published about the role of NEDDylation in CLL together and establishes connections to what is known from other neoplasias, thus providing a new perspective to the underlying mechanisms in CLL.

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Section: Distribution Of the Ubiquitin-like Modifications In Cllmentioning

confidence: 98%

“…complex. In that direction, overexpression of FANCA have been found as a bad prognosis factor in CLL, since it collaborates with MDM2 in the destabilization of p53 (34). Moreover, FANCA is necessary in the NEDDylation of several CLL markers like CXCR5, beta-2-microglobulin and CD44 (35).…”

Section: Distribution Of the Ubiquitin-like Modifications In Cllmentioning

confidence: 98%

A Different View for an Old Disease: NEDDylation and Other Ubiquitin-Like Post-Translational Modifications in Chronic Lymphocytic Leukemia

et al. 2021

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“…In addition to DNA crosslinkers, the FA pathway also confers resistance to DNA alkylating agents in glioma [110]. Alongside FA-mediated drug resistance are observations that FANCA and FANCT/UBE2T correlate with poor prognosis and survival of cancer patients [111,112]. These pre-clinical data highlight the need for development of FA targeted drugs in circumstances where chemotherapy resistance emerges as a result of elevated FA pathway expression and function.…”

Section: Association Of the Fa Pathway With Drug Resistancementioning

confidence: 99%

Fanconi anemia pathway as a prospective target for cancer intervention

Liu

Palovcak

et al. 2020

Cell Biosci

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Fanconi anemia (FA) is a recessive genetic disorder caused by biallelic mutations in at least one of 22 FA genes. Beyond its pathological presentation of bone marrow failure and congenital abnormalities, FA is associated with chromosomal abnormality and genomic instability, and thus represents a genetic vulnerability for cancer predisposition. The cancer relevance of the FA pathway is further established with the pervasive occurrence of FA gene alterations in somatic cancers and observations of FA pathway activation-associated chemotherapy resistance. In this article we describe the role of the FA pathway in canonical interstrand crosslink (ICL) repair and possible contributions of FA gene alterations to cancer development. We also discuss the perspectives and potential of targeting the FA pathway for cancer intervention.

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“…FA gene defects are found in a variety of human cancers. Of the FA genes, FANCA has the highest mutation rate and is associated with AML, pancreatic, cervical, oral and prostate cancers [1,27]. An elevated FANCA expression determines a worse outcome for patients with chronic lymphocytic leukemia (CLL) and is due to a reduction of p53 genes, p21 and ΔNp73 [28].…”

Section: Fa Signaling and Cancermentioning

confidence: 99%

“…An elevated FANCA expression determines a worse outcome for patients with chronic lymphocytic leukemia (CLL) and is due to a reduction of p53 genes, p21 and ΔNp73 [28]. Another group found FANCA amplification correlates with reduced progression-free survival in head and neck squamous cell carcinoma after radiotherapy [27]. FANCC has the next highest mutation rate and is similarly associated with pancreatic, cervical and oral cancers in addition to breast cancer [1,6,29].…”

Section: Fa Signaling and Cancermentioning

confidence: 99%