Toward a therapeutic reduction of imatinib refractory myeloproliferative neoplasm-initiating cells

Philips, Steven; Hildenbrand, Zacariah L.; Oravecz-Wilson, Katherine; Foley, Samantha B.; Mgbemena, Victoria; Ross, Theodora S.

doi:10.1038/onc.2013.484

Cited by 3 publications

(3 citation statements)

References 48 publications

(68 reference statements)

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“…In bone marrow, hematopoietic cells are divided into Lin − c-Kit + (LK) cells enriched for myeloid progenitors and megakaryocyte-erythroid progenitors and LSK cells comprising long-term HSCs, short-term HSCs, and multipotent progenitors (2223). Therefore, we analyzed LK and LSK populations to clarify the developmental impairment of HSCs and hematopoietic progenitor cells in Vav_ Atg5 −/− mice.…”

Section: Resultsmentioning

confidence: 99%

The autophagy Protein Atg5 Plays a Crucial Role in the Maintenance and Reconstitution Ability of Hematopoietic Stem Cells

Jung

Shim

et al. 2019

Immune Netw

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Hematopoietic stem cells (HSCs) in bone marrow are pluripotent cells that can constitute the hematopoiesis system through self-renewal and differentiation into immune cells and red blood cells. To ensure a competent hematopoietic system for life, the maintenance of HSCs is tightly regulated. Although autophagy, a self-degradation pathway for cell homeostasis, is essential for hematopoiesis, the role of autophagy key protein Atg5 in HSCs has not been thoroughly investigated. In this study, we found that Atg5 deficiency in hematopoietic cells causes survival defects, resulting in severe lymphopenia and anemia in mice. In addition, the absolute numbers of HSCs and multiple-lineage progenitor cells were significantly decreased, and abnormal erythroid development resulted in reduced erythrocytes in blood of Vav_ Atg5 −/− mice. The proliferation of Lin − Sca-1 + c-Kit + HSCs was aberrant in bone marrow of Vav_ Atg5 −/− mice, and mature progenitors and terminally differentiated cells were also significantly altered. Furthermore, the reconstitution ability of HSCs in bone marrow chimeric mice was significantly decreased in the presence of Atg5 deficiency in HSCs. Mechanistically, impairment of autophagy-mediated clearance of damaged mitochondria was the underlying cause of the HSC functional defects. Taken together, these results define the crucial role of Atg5 in the maintenance and the reconstitution ability of HSCs.

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Section: Resultsmentioning

confidence: 99%

The autophagy Protein Atg5 Plays a Crucial Role in the Maintenance and Reconstitution Ability of Hematopoietic Stem Cells

Jung

Shim

et al. 2019

Immune Netw

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“…The overlap between two breast cancer datasets was 402 small molecules and showed high consistency. We also furthered the validation analysis by comparing the relationship of small molecules targeting pathways to DrugBank and CTD databases for liver and lung cancers and known targeted therapy results were available in Table S3 [ 43 – 45 ]. The validation results were summarised in Figure 5 .…”

Section: Resultsmentioning

confidence: 99%

Integrated Analysis Identifies Interaction Patterns between Small Molecules and Pathways

Chen

et al. 2014

BioMed Research International

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Previous studies have indicated that the downstream proteins in a key pathway can be potential drug targets and that the pathway can play an important role in the action of drugs. So pathways could be considered as targets of small molecules. A link map between small molecules and pathways was constructed using gene expression profile, pathways, and gene expression of cancer cell line intervened by small molecules and then we analysed the topological characteristics of the link map. Three link patterns were identified based on different drug discovery implications for breast, liver, and lung cancer. Furthermore, molecules that significantly targeted the same pathways tended to treat the same diseases. These results can provide a valuable reference for identifying drug candidates and targets in molecularly targeted therapy.

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“…For example, it is known that drug treatments that have combinations of ATO with imatinib can eliminate CML-initiating cells. In contrast, the same treatment without implementing ATO (only with imatinib) did not show positive results and did not achieve the goal of curing the disease [19]. Also, ATO can be combined with tretinoin (all-transretinoic acid or ATRA) to give complete remission results more significant than 90% in the treatment of CML or with idarubicin for induction therapies [20].…”

Section: Chronic Myeloid Leukemiamentioning

confidence: 99%

Arsenic Trioxide: Pharmacological Applications

Redondo

Salas²,

Zúñiga³

et al. 2023

Vitae

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Background: Arsenic trioxide is a chemical compound that has been used as a treatment for various diseases. Despite being potentially toxic, this compound has been used as a therapy to treat Acute Myeloid Leukemia and is being investigated as a possible treatment for different types of cancer. Objectives: The present review aims to describe the use and studies reported in the literature of Arsenic Trioxide as a possible therapeutic agent for Acute Myeloid Leukemia, Acute Promyelocytic Leukemia, Chronic Myeloid Leukemia, Multiple Myeloma, Myelodysplastic Syndrome, Hepatocellular Carcinoma, Lung Cancer, Neuroblastoma, Breast Cancer, Aplastic Hepatitis C, and HIV-1. Methods: A systematic review was conducted using databases (Elsevier, Google Scholar, PubMed) to compile documents published before December 2023. Results: Multiple pharmacological applications of arsenic trioxide have been reported to treat acute and chronic myeloid leukemia. Arsenic trioxide has been shown to inhibit angiogenesis, which helps treat multiple myeloma. Several studies have shown and suggested the effectiveness of arsenic trioxide as a treatment of hepatocellular carcinoma, lung cancer, neuroblastoma, prostate cancer, breast cancer, aplastic anemia, hepatitis C, and HIV-1.Conclusion: Despite potentially toxic effects, Arsenic compounds are therapeutic agents for multiple diseases, from syphilis to cancer. In recent years, more efficient ways have been investigated to deliver and find the specific dose to treat the disease, causing the fewest possible adverse effects.

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Toward a therapeutic reduction of imatinib refractory myeloproliferative neoplasm-initiating cells

Cited by 3 publications

References 48 publications

The autophagy Protein Atg5 Plays a Crucial Role in the Maintenance and Reconstitution Ability of Hematopoietic Stem Cells

The autophagy Protein Atg5 Plays a Crucial Role in the Maintenance and Reconstitution Ability of Hematopoietic Stem Cells

Integrated Analysis Identifies Interaction Patterns between Small Molecules and Pathways

Arsenic Trioxide: Pharmacological Applications

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