Werner helicase is required for proliferation and DNA damage repair in multiple myeloma

Yildiz, Dilara Akçora; Özkan, Tülin; Özen, Mehmet; Gündüz, Mehmet; Sunguroğlu, Asuman; Beksaç, Meral

doi:10.1007/s11033-022-08178-3

Cited by 2 publications

(2 citation statements)

References 24 publications

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“…Finally, mRNA expression of WRN is also increased in MM patients compared with normal plasma cells. NSC19630, a specific WRN helicase inhibitor, induces increased DNA damage and apoptosis in preclinical models of MM [ 63 ].…”

Section: Ddr and Dna Repair In Normal Tissues And In MMmentioning

confidence: 99%

Understanding DNA Damage Response and DNA Repair in Multiple Myeloma

Petrilla,

Galloway,

Kudalkar

et al. 2023

Cancers

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Multiple myeloma (MM) is a plasma cell malignancy characterized by several genetic abnormalities, including chromosomal translocations, genomic deletions and gains, and point mutations. DNA damage response (DDR) and DNA repair mechanisms are altered in MM to allow for tumor development, progression, and resistance to therapies. Damaged DNA rarely induces an apoptotic response, given the presence of ataxia-telangiectasia mutated (ATM) loss-of-function or mutations, as well as deletions, mutations, or downregulation of tumor protein p53 (TP53) and tumor protein p73 (TP73). Moreover, DNA repair mechanisms are either hyperactive or defective to allow for rapid correction of the damage or permissive survival. Medications used to treat patients with MM can induce DNA damage, by either direct effects (mono-adducts induced by melphalan), or as a result of reactive oxygen species (ROS) production by proteasome inhibitors such as bortezomib. In this review, we will describe the mechanisms of DDR and DNA repair in normal tissues, the contribution of these pathways to MM disease progression and other phenotypes, and the potential therapeutic opportunities for patients with MM.

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Section: Ddr and Dna Repair In Normal Tissues And In MMmentioning

confidence: 99%

Understanding DNA Damage Response and DNA Repair in Multiple Myeloma

Petrilla,

Galloway,

Kudalkar

et al. 2023

Cancers

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“…The Werner syndrome ATP-dependent helicase (WRN) is a RecQ enzyme involved in the maintenance of genome integrity. WRN is associated with Werner syndrome and a predisposition to multiple cancers, such as multiple myeloma [ 28 ], myelodysplastic syndrome/acute myeloid leukemia [ 29 ], colorectal cancer [ 30 ], breast cancer [ 31 ], and ovarian cancer [ 32 ]. WRN contributes to chromosomal stability for survival in both normal and cancer cells [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Renal dysfunction, malignant neoplasms, atherosclerotic cardiovascular diseases, and sarcopenia as key outcomes observed in a three-year follow-up study using the Werner Syndrome Registry

Maeda

Koshizaka

Shoji

et al. 2023

Aging

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Werner syndrome is an adult-onset progeria syndrome that results in various complications. This study aimed to clarify the profile and secular variation of the disease. Fifty-one patients were enrolled and registered in the Werner Syndrome Registry. Their data were collected annually following registration. A cross-sectional analysis at registration and a longitudinal analysis between the baseline and each subsequent year was performed. Pearson's chi-squared and Wilcoxon signed-rank tests were used. Malignant neoplasms were observed from the fifth decade of life (mean onset: 49.7 years) and were observed in approximately 30% of patients during the 3-year survey period. Regarding renal function, the mean estimated glomerular filtration rate calculated from serum creatinine (eGFRcre) and eGFRcys, which were calculated from cystatin C in the first year, were 98.3 and 83.2 mL/min/1.73 m 2 , respectively, and differed depending on the index used. In longitudinal analysis, the average eGFRcre for the first and fourth years was 74.8 and 63.4 mL/min/1.73 m 2 , showing a rapid decline. Secular changes in Werner syndrome in multiple patients were identified. The prevalence of malignant neoplasms is high, and renal function may decline rapidly. It is, therefore, necessary to carry out active and detailed examinations and pay attention to the type and dose of the drugs used.

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Werner helicase is required for proliferation and DNA damage repair in multiple myeloma

Cited by 2 publications

References 24 publications

Understanding DNA Damage Response and DNA Repair in Multiple Myeloma

Understanding DNA Damage Response and DNA Repair in Multiple Myeloma

Renal dysfunction, malignant neoplasms, atherosclerotic cardiovascular diseases, and sarcopenia as key outcomes observed in a three-year follow-up study using the Werner Syndrome Registry

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