Mechanisms of somatic transformation in inherited bone marrow failure syndromes

Choijilsuren, Haruna B; Park, Yeji; Jung, Moonjung

doi:10.1182/hematology.2021000271

Cited by 17 publications

(13 citation statements)

References 50 publications

(57 reference statements)

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“…Due to the rapid renewal of bone marrow hematopoietic cells, ribosome biogenesis is involved in this process. 261 , 262 Therefore, the blood system is more vulnerable to ribosome dysfunction. It has been shown that some blood diseases are associated with ribosome dysfunction.…”

Section: Ribosome and Blood Diseasesmentioning

confidence: 99%

Ribosome biogenesis in disease: new players and therapeutic targets

Jiao

Liu

et al. 2023

Sig Transduct Target Ther

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The ribosome is a multi-unit complex that translates mRNA into protein. Ribosome biogenesis is the process that generates ribosomes and plays an essential role in cell proliferation, differentiation, apoptosis, development, and transformation. The mTORC1, Myc, and noncoding RNA signaling pathways are the primary mediators that work jointly with RNA polymerases and ribosome proteins to control ribosome biogenesis and protein synthesis. Activation of mTORC1 is required for normal fetal growth and development and tissue regeneration after birth. Myc is implicated in cancer development by enhancing RNA Pol II activity, leading to uncontrolled cancer cell growth. The deregulation of noncoding RNAs such as microRNAs, long noncoding RNAs, and circular RNAs is involved in developing blood, neurodegenerative diseases, and atherosclerosis. We review the similarities and differences between eukaryotic and bacterial ribosomes and the molecular mechanism of ribosome-targeting antibiotics and bacterial resistance. We also review the most recent findings of ribosome dysfunction in COVID-19 and other conditions and discuss the consequences of ribosome frameshifting, ribosome-stalling, and ribosome-collision. We summarize the role of ribosome biogenesis in the development of various diseases. Furthermore, we review the current clinical trials, prospective vaccines for COVID-19, and therapies targeting ribosome biogenesis in cancer, cardiovascular disease, aging, and neurodegenerative disease.

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Section: Ribosome and Blood Diseasesmentioning

confidence: 99%

Ribosome biogenesis in disease: new players and therapeutic targets

Jiao

Liu

et al. 2023

Sig Transduct Target Ther

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“…The mutational spectrum in IBMFS is different from that in the general elderly population, as epigenetic regulators, such as DNMT3A, TET2, and ASXL1 , the most frequently mutated genes in the elderly population, are relatively rare. Instead, somatic genomic alterations that can restore the original function of a protein or allow pathological adaptation for survival are preferentially selected for clonal expansion [ 34 ]. Based on current knowledge, unless accompanied by high-risk cytogenetic abnormalities, progressive cytopenia and/or BM morphologic changes, clonal hematopoiesis itself does not require immediate definitive treatment even in the setting of IBMFS [ 34 ].…”

Section: Clonal Hematopoiesis In Inherited Bone Marrow Failure Syndromementioning

confidence: 99%

“…Instead, somatic genomic alterations that can restore the original function of a protein or allow pathological adaptation for survival are preferentially selected for clonal expansion [ 34 ]. Based on current knowledge, unless accompanied by high-risk cytogenetic abnormalities, progressive cytopenia and/or BM morphologic changes, clonal hematopoiesis itself does not require immediate definitive treatment even in the setting of IBMFS [ 34 ].…”

Section: Clonal Hematopoiesis In Inherited Bone Marrow Failure Syndromementioning

confidence: 99%

Overview of inherited bone marrow failure syndromes

Park

2022

Blood Res

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Patients with inherited bone marrow failure syndrome (IBMFS) can develop peripheral blood cytopenia, which can ultimately progress to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Although some cases of IBMFS are diagnosed based on their typical presentation, variable disease penetrance and expressivity may result in diagnostic dilemmas. With recent advances in genomic evaluation including next-generation sequencing, many suspected cases of IBMFS with atypical presentations can be identified. Identification of the genetic causes of IBMFS has led to important advances in understanding DNA repair, telomere biology, ribosome biogenesis, and hematopoietic stem cell regulation. An overview of this syndromes is summarized in this paper.

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“…Patients with FA have a 30% to 40% cumu la tive risk of mye loid malig nan cies by age 40 years. 17,18 These often arise from clonal kar yo type abnor mal i ties and unbal anced trans lo ca tions, lead ing to gains or losses of chro mo somes. Some cyto ge netic changes pre dict neg a tive out comes, and their iden ti fi ca tion is impor tant to decide the tim ing of HSCT 19,20 (Figure 1).…”

Section: Clonal Evo Lu Tionmentioning

confidence: 99%

“…ily indi cate impending trans for ma tion. 18 Conversely, mono somy 7/del(7q) is con sid ered a marker of trans for ma tion, requir ing urgent HSCT. 18 Other cyto ge netic changes indi cat ing a poor prog no sis are gain of chro mo some 3q, fre quently pre ced ing mono somy 7/del(7q), 21,22 and RUNX1 abnor mal i ties, includ ing cryp tic trans lo ca tions, that also indi cate imme di ate HSCT.…”

Section: Search Of Hla-matched Unre Lated Donor If No Healthy Hla-mat...mentioning

confidence: 99%

Modern management of Fanconi anemia

Dufour

Pierri

2022

Hematology

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In this review, we present a clinical case report and discussion to outline the importance of long-term specific Fanconi anemia (FA) monitoring, and we discuss the main aspects of the general management of patients with FA and clinical complications. While several nontransplant treatments are currently under evaluation, hematopoietic stem cell transplantation (HSCT) remains the only therapeutic option for bone marrow failure (BMF). Although HSCT outcomes in patients with FA have remarkably improved over the past 20 years, in addition to the mortality intrinsic to the procedure, HSCT increases the risk and accelerates the appearance of late malignancies. HSCT offers the best outcome when performed in optimal conditions (moderate cytopenia shifting to severe, prior to transfusion dependence and before clonal evolution or myelodysplasia/acute myeloid leukemia); hence, an accurate surveillance program is vital. Haploidentical HSCT offers very good outcomes, although long-term effects on malignancies have not been fully explored. A monitoring plan is also important to identify cancers, particularly head and neck carcinomas, in very early phases. Gene therapy is still experimental and offers the most encouraging results when performed in early phases of BMF by infusing high numbers of corrected cells without genotoxic effects. Patients with FA need comprehensive monitoring and care plans, coordinated by centers with expertise in FA management, that start at diagnosis and continue throughout life. Such long-term follow-up is essential to detect complications related to the disease or treatment in this setting.

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Mechanisms of somatic transformation in inherited bone marrow failure syndromes

Cited by 17 publications

References 50 publications

Ribosome biogenesis in disease: new players and therapeutic targets

Ribosome biogenesis in disease: new players and therapeutic targets

Overview of inherited bone marrow failure syndromes

Modern management of Fanconi anemia

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