Antioxidant N-acetyl-l-cysteine increases engraftment of human hematopoietic stem cells in immune-deficient mice

Hu, Linping; Cheng, Hui; Gao, Yingdai; Shi, Ming; Liu, Yanfeng; Hu, Zheng; Xu, Jing; Qiu, Lugui; Yuan, Weiping; Leung, Anskar Y. H.; Yang, Yong‐Guang; Cheng, Tao

doi:10.1182/blood-2014-03-559369

Cited by 75 publications

(65 citation statements)

References 13 publications

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“…Apoptosis inhibition might be feasible at different levels of the signaling cascade: (a) engagement of upstream protective pathways (i.e., cytokines); (b) inhibition of detrimental signals (i.e., ROS inhibition); or (c) modulation of Bcl-2 protein levels. In contrast, apoptosis inhibition on a more downstream level (i.e., caspase activation) might not be sufficient to ensure survival as noncaspasedependent forms of cell death could be engaged upon mitochondrial damage [159,160].…”

Section: Hematopoietic Stem Cell Transplantationmentioning

confidence: 99%

Bcl‐2 proteins in development, health, and disease of the hematopoietic system

et al. 2016

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Members of the Bcl‐2 protein family regulate cell fate decisions following a variety of developmental cues or stress signals, with the outcomes of cell death or survival, thus shaping multiple mammalian tissues. This review describes in detail how anti‐ and proapoptotic Bcl‐2 proteins contribute to the development and functioning of the fetal and adult hematopoietic systems and how they influence the generation and maintenance of different hematopoietic lineages. An overview on how stress signals such as genotoxic stress or inflammation can compromise blood cell production, partially by engaging the intrinsic apoptosis pathway, is presented. Finally, the review describes how Bcl‐2 protein deregulation—either leading to increased apoptosis resistance or excessive cell death—contributes to many hematological disorders, with specific focus on rare disorders of hematopoiesis and how this knowledge may be used therapeutically.

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Section: Hematopoietic Stem Cell Transplantationmentioning

confidence: 99%

Bcl‐2 proteins in development, health, and disease of the hematopoietic system

et al. 2016

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“…*: P < 0.05, **: P < 0.01, ***: P < 0.001, ns: not significant. Accumulation of ROS is reported to compromise HSC activity [19][20][21]. On the other hand, recent studies have suggested that ROS play an important role in differentiation of HSCs, especially during the early stages of hematopoietic reconstitution after transplantation [22][23].…”

Section: Discussionmentioning

confidence: 99%

Reactive oxygen species in hematopoietic stem cells affect culture outcomes under inflammatory conditions

Ishida¹,

Yamazaki²,

Nakauchi³

et al. 2015

Open J Hematol

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“…New biological insights have led to improved engraftment of human hematopoietic cells in the NOD/SCID mouse. 17 Transgenic strains of the conventional NOD/SCID mouse are better able to engraft primary human AML isolates. 18 Within the constraints of translating human doses to mouse doses, treatment of new xenograft and genetically engineered mouse models with doxorubicin and cytarabine reproduce important aspects of AML therapy including kinetics of response/resistance, quantifiable residual disease, and greater responsiveness of pretreatment patient samples than of samples from patients with relapsed disease.…”

Section: Issue 1: Preclinical Studies: Limitations and Newer Approachesmentioning

confidence: 99%

Current challenges in clinical development of “targeted therapies”: the case of acute myeloid leukemia

Estey

Levine

Löwenberg

2015

Blood

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A fundamental difficulty in testing “targeted therapies” in acute myeloid leukemia (AML) is the limitations of preclinical models in capturing inter- and intrapatient genomic heterogeneity. Clinical trials typically focus on single agents despite the routine emergence of resistant subclones and experience in blast-phase chronic myeloid leukemia and acute promyelocytic leukemia arguing against this strategy. Inclusion of only relapsed-refractory, or unfit newly diagnosed, patients risks falsely negative results. There is uncertainty as to whether eligibility should require demonstration of the putative target and regarding therapeutic end points. Although use of in vivo preclinical models employing primary leukemic cells is first choice, newer preclinical models including “organoids” and combinations of pharmacologic and genetic approaches may better align models with human AML. We advocate earlier inclusion of combinations ± chemotherapy and of newly diagnosed patients into clinical trials. When a drug plausibly targets a pathway uniquely related to a specific genetic aberration, eligibility should begin with this subset, including patients with other malignancies, with subsequent extension to other patients. In other cases, a more open-minded approach to initial eligibility would facilitate quicker identification of responsive subsets. Complete remission without minimal residual disease seems a particularly useful short-term end point. Genotypic and phenotypic studies should be prespecified and performed routinely to distinguish responders from nonresponders.

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Antioxidant N-acetyl-l-cysteine increases engraftment of human hematopoietic stem cells in immune-deficient mice

Abstract: Key Points NAC increases engraftment of human hematopoietic stem cells in immunodeficient mice.

Cited by 75 publications

References 13 publications

Bcl‐2 proteins in development, health, and disease of the hematopoietic system

Bcl‐2 proteins in development, health, and disease of the hematopoietic system

Reactive oxygen species in hematopoietic stem cells affect culture outcomes under inflammatory conditions

Current challenges in clinical development of “targeted therapies”: the case of acute myeloid leukemia

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