S-phase fraction as a useful marker for prognosis and therapeutic response in patients with aplastic anemia

Tripathi, Anil Kumar; Tripathi, Payal; Kumar, Ashutosh; Ahmad, Rizwan; Singh, Raj Kumar; Balapure, Anil K.; Vishwakerma, Achchhe Lal

doi:10.1016/s1658-3876(08)50007-0

Cited by 3 publications

(3 citation statements)

References 34 publications

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“…SPF is considered as an additional objective parameter for predicting the therapeutic response. A large number of studies have demonstrated the prognostic significance of FC analyses of SPF in many cancer types [42,43]. Smets et al reported that ALL patients with SPF…”

Section: Discussionmentioning

confidence: 99%

Multicolor flow cytometry immunophenotyping and characterization of aneuploidy in pediatric B-cell precursor acute lymphoblastic leukemia

Pierzyna-Świtała¹,

Sędek²,

Kulis³

et al. 2021

cejoi

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the aim of this study was to assess the incidence of dna aneuploidy in Polish children with B-cell precursor acute lymphoblastic leukemia (BcP-all) and the relationship between aneuploidy and immunological phenotype, age, leukocyte count, s-phase fraction (sPF) and early response to induction chemotherapy assessed by the percentage of residual blast cells in bone marrow aspirates. the study group consisted of 267 patients. dna content and immunophenotype were assessed in the bone marrow before treatment using multicolor flow cytometry (Fc). dna aneuploidy was detected in 50/267 (19%) patients. high hyperdiploidy was found to be associated with lower leukocyte count (p = 0.006) and common all immunophenotype. Flow cytometry analysis revealed that high hyperdiploid BcP-all patients showed significantly higher expression of cd9, cd20, cd22, cd58, cd66c, cd86 and cd123 antigens as compared to other groups of ploidy. in contrast, cd45 showed decreased expression. the percentage of leukemic blasts at diagnosis was lower in high hyperdiploid BcP-all cases than in diploid (79% vs. 85.7%, p = 0.001). the difference in minimal residual disease (Mrd) levels on day 15 and 33 of induction therapy between analyzed groups was not significant.this study showed that high hyperdiploidy is associated with lower wBc count and specific immunological phenotype. Flow cytometric evaluation of expression of selected antigens can be used for fast identification of markers of aneuploidy in pediatric BcP-all, before genetic tests results are available. understanding the biological significance of aneuploidy in leukemia can potentially be exploited therapeutically using targeted therapies against specific blast cell subclones.

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Section: Discussionmentioning

confidence: 99%

Multicolor flow cytometry immunophenotyping and characterization of aneuploidy in pediatric B-cell precursor acute lymphoblastic leukemia

Pierzyna-Świtała¹,

Sędek²,

Kulis³

et al. 2021

cejoi

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“…Circulating hematopoietic progenitors were shown to increase more dramatically in younger patients after cardiopulmonary bypass graft than in older patients, and advanced age was associated with impaired coronary microvascular response to vascular endothelial growth factor (VEGF) [29]. Conversely, advanced age has been associated with a higher S-phase fraction of circulating HSCs in patients with aplastic anemia, but this predisposed them to dysplasia and conversion to acute myeloid leukemia, indicative of abnormal HSC function [30]. Studies of adult stem cell isolation yield in elderly individuals have shown that equivalent numbers of adipose-derived mesenchymal stem cells (MSCs) can be isolated from older individuals undergoing vascular surgical procedures as from young, healthy individuals [31,32].…”

Section: Adults Stem Cells and Causes Of Agingmentioning

confidence: 99%

Adult Stem Cells and Diseases of Aging

Boyette

Tuan

2014

JCM

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Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan.

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“…35 Conversely, advanced age has been associated with a higher S-phase fraction of circulating HSCs in patients with aplastic anemia, but this predisposed them to dysplasia and conversion to acute myeloid leukemia, indicative of abnormal HSC function. 36 Studies of adult stem cell isolation yield in elderly individuals have shown that equivalent numbers of adipose-derived MSCs can be isolated from older individuals undergoing vascular surgical procedures as from young, healthy individuals, 37,38 but the question remains whether those cells can be adequately expanded in tissue culture and whether they are able to mobilize, proliferate, and effect tissue repair in vivo when they are needed. In fact these same studies have shown that while advanced age does not impact availability of stem cells, fat from patients with diabetes yielded significantly fewer stem cells than fat from non-diabetic patients, suggesting that stem cells in the context of aging should probably be considered distinctly from stem cells in the context of diseases of aging.…”

Section: Adult Stem Cells and Diseases Of Agingmentioning

confidence: 99%

Altering Fate Determination of Human Bone Marrow-Derived Mesenchymal Stem Cells through Environmental and Transcriptional Cues

Boyette

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i Abstract Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling and premature senescence as a response to oncogenic insults to the somatic genome both contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments.Stem cells are promising candidate cells for regenerative applications because they possess high proliferative capacity and the potential to differentiate into other cell types.Mesenchymal stem cells (MSCs) are easily sourced but do not retain their proliferative and multi-lineage differentiative capabilities after prolonged ex vivo propagation. We investigated the use of hypoxia as a preconditioning agent and in differentiating cultures to enhance MSC function. Culture in 5% ambient O2 consistently enhanced clonogenic potential of primary MSCs from all donors tested. We determined that enhanced clonogenicity was attributable to increased proliferation, increased vascular endothelial growth factor (VEGF) secretion, and increased matrix turnover. Hypoxia did not impact the incidence of cell death. Application of hypoxia to osteogenic cultures resulted in enhanced total mineral deposition, although this effect was only detected in MSCs preconditioned in normoxic conditions. Osteogenesisassociated genes were up-regulated in hypoxia, and alkaline phosphatase activity was enhanced. Adipogenic differentiation was inhibited by exposure to hypoxia during differentiation. Chondrogenesis in 3-dimensional (3D) pellet cultures was inhibited by preconditioning with hypoxia. However, in cultures expanded under normoxia, hypoxia ii applied during subsequent pellet culture enhanced chondrogenesis. While hypoxic preconditioning appears to be an excellent way to expand a highly clonogenic progenitor pool, our findings suggest that it may blunt the differentiation potential of MSCs, compromising their utility for regenerative tissue engineering. Exposure to hypoxia during differentiation (post normoxic expansion), however, appears to result in a greater quantity of functional osteoblasts and chondrocytes and ultimately a larger quantity of high quality differentiated tissue.Media formulations for MSC culture and differentiation vary between labs; two notable variables addressed inconsistently in the field are ascorbate supplementation and glucose concentration in MSC expansion medium. Glucose and ascorbate effects are coupled to the Hif1α pathway. Therefore, we examined the effects of ascorbate supplementation and low versus high glucose medium in the settings of hypoxia and normoxia on colony formation, colony morphology, proliferation, VEGF secretion, and senescence of MSCs. We found that there is no one medium formulation that maximizes MSC performance for all of these assays.Depending on the desired outcome of the culture, t...

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S-phase fraction as a useful marker for prognosis and therapeutic response in patients with aplastic anemia

Cited by 3 publications

References 34 publications

Multicolor flow cytometry immunophenotyping and characterization of aneuploidy in pediatric B-cell precursor acute lymphoblastic leukemia

Multicolor flow cytometry immunophenotyping and characterization of aneuploidy in pediatric B-cell precursor acute lymphoblastic leukemia

Adult Stem Cells and Diseases of Aging

Altering Fate Determination of Human Bone Marrow-Derived Mesenchymal Stem Cells through Environmental and Transcriptional Cues

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