Regulation of Hematopoietic Stem Cell Fate and Malignancy

Cho, Hee Jun; Lee, Jungwoon; Yoon, Suk Ran; Lee, Hee Gu; Jung, Hye Young

doi:10.3390/ijms21134780

Cited by 13 publications

(8 citation statements)

References 164 publications

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“…In this study, 46% of cases had positive C-MYC protein expression, while 58% had high Ki-67 PI. This result was close to the ratio (47.6%) detected by Yun et al, and to the ratio (42%) reported by Julum et al, as regards IHC of C-MYC protein expression [11][12][13][14][15][16][17][18][19][20][21][22][23]. In this study, C-MYC protein expression was significantly associated with high Ki-67 PI.…”

Section: Discussionsupporting

confidence: 91%

“…The role of C-MYC oncogene in the subtypes of B-cell lymphomas was clarified by many previous studies. In Burkitt's lymphoma, the translocation of C-MYC at 14q32 is the most common, and occurring in approximately 80% of cases [20]. In plasmablastic lymphoma C-MYC rearrangements, most commonly t (8; 14) (q24•1; q32) are found in approximately 49% of cases [21].…”

Section: Discussionmentioning

confidence: 99%

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C-MYC Protein Expression and High Ki-67 Proliferative Index are Predictives of Disease Relapse in Diffuse Large B Cell Lymphoma

El-Hussien

Mokhtar

Khorshed

2021

Asian Pac J Cancer Biol

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Objective: To evaluate the status of C-MYC protein expression and Ki-67 proliferative index and to clarify their role in predicting relapse of diffuse large B cell lymphoma (DLBL). Materials and Methods: A retrospective study conducted on 50 cases diagnosed as DLBL in a 3 years’ time period from January 2014 till December 2016, collected from the archive of Pathology Departments of the National Cancer Institute Cairo - Egypt, Misr University for Science and Technology and private labs of authors. The diagnosis of DLBL for all cases, both nodal and extranodal, was confirmed by histopathologic examination and immunophenotyping. Automated immunohistochemical staining using antibodies against C-MYC protein and MIB-1 was used to evaluate the C-MYC expression in tumor cells and to assess their proliferative ability by calculating Ki-67 labelling index. The relation between the percentage of C-MYC protein expression, Ki-67 proliferative index, clinical data and the relapse status during the follow up period were analyzed. Results: A total of 50 cases of DLBL in both nodal and extra-nodal sites were included. Twenty-three cases (46%) were expressing the C-MYC protein, and 29 cases (58%) showed high Ki-67 proliferative index. Twenty-two cases (44%) relapsed during the follow-up period. Positive C-MYC protein expression was significantly associated with high Ki-67 proliferative index. C-MYC protein expression and high Ki-67 proliferative index were independently associated with disease relapses in 81.8% and 86.4% of cases respectively. Cases with combined C-MYC protein expression and high Ki-67 proliferative index showed statistical prediction of relapse in 81.8% of cases. Conclusion: C-MYC protein expression and high Ki-67 proliferative index were independently associated with relapse of diffuse large B cell lymphoma. Furthermore, the combined positive C-MYC protein expression and high Ki-67 proliferative index is better than a single positive test in predicting relapses among DLBL patients.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

C-MYC Protein Expression and High Ki-67 Proliferative Index are Predictives of Disease Relapse in Diffuse Large B Cell Lymphoma

El-Hussien

Mokhtar

Khorshed

2021

Asian Pac J Cancer Biol

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“…Importantly, the pathways involved in the self-renewal HSCs regulate the levels of ROS, emphasising the importance of redox homeostasis in haematopoiesis. In addition, multiple other proteins and pathways, such as tumour suppressors p53 (TP53) and retinoblastoma protein (RB), glycogen synthase kinase-3 (GSK-3), cyclin dependent kinases (CDK), and BCL2 all play an important role in self-renewal, maintaining quiescence, proliferation, differentiation and survival of HSCs mainly through the modulation of mitochondrial ROS [85]. ROS, therefore, plays an essential role in the quiescence, self-renewal, and long-term survival of HSCs, and hence, elevated, and sustained ROS exposure is likely to contribute to cell cycle progression, DNA damage and the initiation and progression of ALL.…”

Section: The Essential Role Of Ros In the Maintenance Of Haemopoietic Stem Cells (Hscs) And Innate And Adaptive Immunitymentioning

confidence: 99%

Reactive Oxygen Species in Acute Lymphoblastic Leukaemia: Reducing Radicals to Refine Responses

et al. 2021

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Acute lymphoblastic leukaemia (ALL) is the most common cancer diagnosed in children and adolescents. Approximately 70% of patients survive >5-years following diagnosis, however, for those that fail upfront therapies, survival is poor. Reactive oxygen species (ROS) are elevated in a range of cancers and are emerging as significant contributors to the leukaemogenesis of ALL. ROS modulate the function of signalling proteins through oxidation of cysteine residues, as well as promote genomic instability by damaging DNA, to promote chemotherapy resistance. Current therapeutic approaches exploit the pro-oxidant intracellular environment of malignant B and T lymphoblasts to cause irreversible DNA damage and cell death, however these strategies impact normal haematopoiesis and lead to long lasting side-effects. Therapies suppressing ROS production, especially those targeting ROS producing enzymes such as the NADPH oxidases (NOXs), are emerging alternatives to treat cancers and may be exploited to improve the ALL treatment. Here, we discuss the roles that ROS play in normal haematopoiesis and in ALL. We explore the molecular mechanisms underpinning overproduction of ROS in ALL, and their roles in disease progression and drug resistance. Finally, we examine strategies to target ROS production, with a specific focus on the NOX enzymes, to improve the treatment of ALL.

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“…Thus, HSC quiescence is crucial for sustaining the HSC pool and protects the HSCs by minimizing replication-associated mutations in their genome. 13 The concept of the HSC niche was proposed to define the cellular interactions and molecular pathways that underlie the regulation of quiescence or activation of individual HSCs by their BM microenvironment.…”

Section: The Hematopoietic Nichesmentioning

confidence: 99%

The Impact of Sedentary Lifestyle, High-fat Diet, Tobacco Smoke, and Alcohol Intake on the Hematopoietic Stem Cell Niches

Kaastrup

Grønbæk

2021

HemaSphere

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Hematopoietic stem and progenitor cells maintain hematopoiesis throughout life by generating all major blood cell lineages through the process of self-renewal and differentiation. In adult mammals, hematopoietic stem cells (HSCs) primarily reside in the bone marrow (BM) at special microenvironments called “niches.” Niches are thought to extrinsically orchestrate the HSC fate including their quiescence and proliferation. Insight into the HSC niches mainly comes from studies in mice using surface marker identification and imaging to visualize HSC localization and association with niche cells. The advantage of mouse models is the possibility to study the 3-dimensional BM architecture and cell interactions in an intact traceable system. However, this may not be directly translational to human BM. Sedentary lifestyle, unhealthy diet, excessive alcohol intake, and smoking are all known risk factors for various diseases including hematological disorders and cancer, but how do lifestyle factors impact hematopoiesis and the associated niches? Here, we review current knowledge about the HSC niches and how unhealthy lifestyle may affect it. In addition, we summarize epidemiological data concerning the influence of lifestyle factors on hematological disorders and malignancies.

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Regulation of Hematopoietic Stem Cell Fate and Malignancy

Cited by 13 publications

References 164 publications

C-MYC Protein Expression and High Ki-67 Proliferative Index are Predictives of Disease Relapse in Diffuse Large B Cell Lymphoma

C-MYC Protein Expression and High Ki-67 Proliferative Index are Predictives of Disease Relapse in Diffuse Large B Cell Lymphoma

Reactive Oxygen Species in Acute Lymphoblastic Leukaemia: Reducing Radicals to Refine Responses

The Impact of Sedentary Lifestyle, High-fat Diet, Tobacco Smoke, and Alcohol Intake on the Hematopoietic Stem Cell Niches

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