Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34− fraction

Taussig, David; Vargaftig, Jacques; Miraki-Moud, Farideh; Griessinger, Emmanuel; Sharrock, Kirsty; Luke, Tina; Lillington, Debra M.; Oakervee, Heather; Cavenagh, Jamie; Agrawal, Samir; Lister, T. A.; Gribben, John G.; Bonnet, Dominique

doi:10.1182/blood-2009-02-206565

Cited by 310 publications

(300 citation statements)

References 33 publications

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“…The percentage of CLEC12A + cells in the CD34 + CD38 − compartment in MDS was comparable to the level found in CD34‐positive AML. Conversely, expression of CLEC12A was not found on the CD34 + CD38 − cells in CD34‐negative AML, which is consistent with previous findings indicating that in CD34‐negative AML, the small fraction of CD34‐positive cells in most cases represents normal HSCs (van der Pol et al , 2003; Taussig et al , 2010). Furthermore, and importantly, we showed that the CD34 + CD38 − CLEC12A + cells are indeed malignant and possess functional stem cell properties in terms of self‐renewal when evaluated in the LTC‐IC assay.…”

Section: Discussionsupporting

confidence: 90%

Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome

et al. 2016

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SummaryEvidence of distinct disease propagating stem cells in myelodysplastic syndrome (MDS) has emerged in recent years. However, immunophenotypic characterization of these cancer stem cells remains sparse. In acute myeloid leukaemia (AML), we have previously described aberrant expression of the C‐type lectin domain family 12, member A (CLEC12A) as a stable and reliable marker of leukaemia blasts and as a tool for assessing minimal residual disease. Furthermore, CLEC12A has been proposed as a promising marker of leukaemic stem cells in AML. The role of CLEC12A in MDS, however, remains to be elucidated. In this study, we found CLEC12A aberrantly expressed on the CD34+ CD38− cell compartment in 71% (22/31) of MDS patients, distributed across all Revised International Prognostic Scoring System risk groups. We showed that the CD34+ CD38− CLEC12A+ cells were indeed malignant and possessed functional stem cell properties in the long‐term colony‐initiating cell assay. As opposed to reported findings in AML, we showed that cancer stem cells from MDS samples derived from both CLEC12A positive and negative CD34+ CD38− subpopulations. Due to the absence of CLEC12A on normal haematopoietic stem cells, CLEC12A stem cell immunophenotyping may contribute to diagnosing and monitoring MDS patients and could furthermore add knowledge about disease propagating cells in MDS.

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Section: Discussionsupporting

confidence: 90%

Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome

et al. 2016

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“…For example, CD34 + CD38 + AML cells, as well as CD34 + CD38 − AML cells, both frequently show CSC activity when transplanted into non-obese diabetic, severe combined immunodeficient (NOD/SCID) mice lacking a functional IL2RG chain (NSG or NOG) mice, although previously, this property seemed to be mostly restricted to the CD34 + CD38 − subset when less immunodeficient NOD/SCID mice were used as recipients 38,39 . Nevertheless, a hierarchy of cells can still be found to exist within these leukaemias 40 .…”

Section: When a Clonal Hierarchy Is In Questionmentioning

confidence: 99%

Cancer stem cell definitions and terminology: the devil is in the details

Valent

Bonnet

Maria³

et al. 2012

Nat Rev Cancer

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604

547

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| The cancer stem cell (CSC) concept has important therapeutic implications, but its investigation has been hampered both by a lack of consistency in the terms used for these cells and by how they are defined. Evidence of their heterogeneous origins, frequencies and their genomic, as well as their phenotypic and functional, properties has added to the confusion and has fuelled new ideas and controversies. Participants in The Year 2011 Working Conference on CSCs met to review these issues and to propose a conceptual and practical framework for CSC terminology. More precise reporting of the parameters that are used to identify CSCs and to attribute responses to them is also recommended as key to accelerating an understanding of their biology and developing more effective methods for their eradication in patients. PERSPECTIVES NATURE REVIEWS | CANCER VOLUME 12 | NOVEMBER 2012 | 767

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“…It is not clear whether these antibodies interfere with BM homing or stimulation of intracellular signaling or through Fc-mediated clearance of antibody-labeled cells (22). Furthermore, Taussig et al have observed that both CD34 -and CD34 + fractions from the majority of primary NPM1-mutated AML contained LSCs (25). Taken together, these results challenge the original phenotypic description of LSCs.…”

Section: Introductionmentioning

confidence: 97%

Human acute myelogenous leukemia stem cells are rare and heterogeneous when assayed in NOD/SCID/IL2Rγc-deficient mice

Sarry¹,

Murphy²,

Perry³

et al. 2011

J. Clin. Invest.

338

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Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34− fraction

Abstract: Leukemia-initiating cells (LICs

Cited by 310 publications

References 33 publications

Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome

Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome

Cancer stem cell definitions and terminology: the devil is in the details

Human acute myelogenous leukemia stem cells are rare and heterogeneous when assayed in NOD/SCID/IL2Rγc-deficient mice

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