Different subsets of primary chronic myeloid leukemia stem cells engraft immunodeficient mice and produce a model of the human disease

Eisterer, Wolfgang; Jiang, Xiaoyan; Christ, Oliver; Glimm, Hanno; Lee, K H; Pang, Emily; Lambie, Karen; Shaw, Georgina; Holyoake, Tessa L.; Petzer, Andreas; Auewarakul, Chirayu; Barnett, M. J.; Eaves, Connie J.; Eaves, Allen C.

doi:10.1038/sj.leu.2403649

Cited by 132 publications

(104 citation statements)

References 37 publications

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“…The notion that basophils express substantial amounts of CD26 on their surface suggests that these cells may also be involved in SDF‐1 degradation and in the related migratory defect of CML LSC against this cytokine. Indeed, normal and CML stem cells express CXCR4, the receptor for SDF‐1; and disruption of SDF‐1 activity is considered to lead to stem cell mobilization 71, 72, 76, 77, 78. In this regard, it is worth noting that in patients with severe allergies where basophils may also increase, the numbers of circulating colony‐forming progenitor cells also increase 79.…”

Section: Possible Role Of Basophils In Modulating Stem Cell‐niche Intmentioning

confidence: 99%

The underestimated role of basophils in Ph⁺ chronic myeloid leukaemia

Valent

Horny

Arock

2018

Eur J Clin Investigation

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Chronic myeloid leukaemia (CML) is a hematopoietic neoplasm defined by the chromosome translocation t(9;22) and the related oncogene, BCR‐ABL1. In most patients, leukaemic cells can be kept under control using BCR‐ABL1‐targeting drugs. However, many patients relapse which remains a clinical challenge. In particular, patients with advanced (accelerated or blast phase) CML have a poor prognosis. So far, little is known about molecular and cellular interactions and features that contribute to disease progression and drug resistance in CML. One key prognostic factor at diagnosis is marked basophilia. However, although basophils are well‐known multifunctional effector cells, their impact in CML remains uncertain. In this article, we discuss the potential role of basophils as active contributors to disease evolution and progression in CML. In particular, basophils serve as a unique source of inflammatory, angiogenic and fibrogenic molecules, such as vascular endothelial growth factor or hepatocyte growth factor. In addition, basophils provide vasoactive substances, like histamine as well as the cytokine‐degrading enzyme dipeptidyl‐peptidase IV which may promote stem cell mobilization and the extramedullary spread of stem and progenitor cells. Finally, basophils may produce autocrine growth factors for myeloid cells. Understanding the role of basophils in CML evolution and progression may support the development of more effective treatment concepts.

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Section: Possible Role Of Basophils In Modulating Stem Cell‐niche Intmentioning

confidence: 99%

The underestimated role of basophils in Ph⁺ chronic myeloid leukaemia

Valent

Horny

Arock

2018

Eur J Clin Investigation

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“…9,10 What was not appreciated at the time was the co-mobilization of high numbers of primitive leukemic cells into the blood of such patients. [11][12][13] However, continued cytogenetic follow-up of CML patients' cells showed that the oncogenic process in this disease is indeed one of clonal evolution. As discussed below, we now understand that this process is derivative of an acquired genomic instability that leads to the continuous acquisition of new genetic alterations and an accompanying selection of growthadvantaged subclones, the properties of which may differentially affect treatment response, as well as disease progression.…”

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confidence: 99%

Insights into the stem cells of chronic myeloid leukemia

et al. 2010

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Chronic myeloid leukemia (CML) has long served as a paradigm for generating new insights into the cellular origin, pathogenesis and improved approaches to treating many types of human cancer. Early studies of the cellular phenotypes and genotypes represented in leukemic populations obtained from CML patients established the concept of an evolving clonal disorder originating in and initially sustained by a rare, multipotent, self-maintaining hematopoietic stem cell (HSC). More recent investigations continue to support this model, while also revealing new insights into the cellular and molecular mechanisms that explain how knowledge of CML stem cells and their early differentiating progeny can predict the differing and variable features of chronic phase and blast crisis. In particular, these emphasize the need for new agents that effectively and specifically target CML stem cells to produce non-toxic, but curative therapies that do not require lifelong treatments.

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“…Pas sûr, mais pas facile ! Les arguments initiaux en faveur de la réalité de CSC proviennent de l'analyse de certaines leucémies myéloïdes [2,3], où une petite sous-population (< 0,001%) de cellules, de phénotype CD34 + /CD38 -(un phénotype que partagent aussi les CS hématopoïétiques normales), est seule capable de générer les populations postmitotiques cancéreuses après injection à des souris immunodéficientes NOD-SCID, alors que le reste des cellules leucémi-ques en est incapable ; des arguments convaincants ont aussi été obtenus dans quelques tumeurs solides, notamment les glioblastomes et dans ce cas, les CSC se distinguent par l'expression de l'antigène CD133 [4]. À partir de ces expériences pionnières, le concept de cellules souches cancéreuses s'est propagé comme une traînée de poudre sans toutefois être toujours validé expérimentalement de façon rigoureuse, ce qui est plus difficile dans les cancers solides que dans les hémopathies, les cellules leucémiques étant facilement accessibles dans le sang ou la moelle osseuse, et la hiérarchie hématopoïétique solidement établie.…”

Section: Le Dogme Des Cellules Souches Cancéreusesunclassified