A clinically relevant population of leukemic CD34+CD38− cells in acute myeloid leukemia

Gerber, Jonathan M.; Smith, B. Douglas; Ngwang, Brownhilda; Zhang, Hao; Vala, Milada S.; Morsberger, Laura; Galkin, Steven; Collector, Michael I.; Perkins, Brandy; Levis, Mark J.; Griffin, Constance A.; Sharkis, Saul J.; Borowitz, Michael J.; Karp, Judith E.; Jones, Richard J.

doi:10.1182/blood-2011-06-364182

Cited by 197 publications

(205 citation statements)

References 37 publications

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“…These challenges may result from residual cancer stem cells, which may be resistant to conventional chemo-and radiotherapies and are therefore difficult to eradicate. Gerber et al demonstrated, for the first time, that the presence of CSCs in AML correlates with a poor clinical outcome and suggested that those cells may be responsible for tumor relapse [40]. Therefore, these cells could be responsible for the selection of drug-resistant clones and the eventual development of multidrug resistance (Fig.…”

Section: Cancer Stem Cells-past and Currentmentioning

confidence: 99%

Targeted therapy aimed at cancer stem cells: Wilms’ tumor as an example

2013

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Wilms' tumor (WT), a common renal pediatric solid tumor, serves as a model for a malignancy formed by renal precursor cells that have failed to differentiate properly. Here we review recent evidence showing that the tumors' heterogeneous cell population contains a small fraction of cancer stem cells (CSC) identified by two markers: Neural Cell Adhesion Molecule 1 (NCAM1) expression and Aldehyde dehydrogenase 1 (ALDH1) enzymatic activity. In vivo studies show these CSCs to both self-renew and differentiate to give rise to all tumor components. Similar to other malignancies, the identification of a specific CSC fraction has allowed the examination of a novel targeted therapy, aimed at eradicating the CSC population. The loss of CSCs abolishes the tumor's ability to sustain and propagate, hence, causing tumor degradation with minimal damage to normal tissue.

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Section: Cancer Stem Cells-past and Currentmentioning

confidence: 99%

Targeted therapy aimed at cancer stem cells: Wilms’ tumor as an example

2013

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“…In both normal BM and in the majority of AML BM cells, the CD34+/CD38−/ALDH high population is considered to contain only HSC [21,29,30]. In contrast to normal BM, in AML a second population can be discriminated with cells having intermediate ALDH expression [29]. When purified, this population was most potent in AML engraftment in immunodeficient mice and was generally found positive for leukemic cytogenetic markers [29].…”

Section: Identification Of Leukemic Stem Cellsmentioning

confidence: 99%

“…In normal BM CD34+/CD38− HSC display high levels ALDH activity (ALDH high ) [29]. In both normal BM and in the majority of AML BM cells, the CD34+/CD38−/ALDH high population is considered to contain only HSC [21,29,30]. In contrast to normal BM, in AML a second population can be discriminated with cells having intermediate ALDH expression [29].…”

Section: Identification Of Leukemic Stem Cellsmentioning

confidence: 99%

“…ALDH is shown to protect against DNA damage induced by reactive oxygen species and reactive aldehydes. In normal BM CD34+/CD38− HSC display high levels ALDH activity (ALDH high ) [29]. In both normal BM and in the majority of AML BM cells, the CD34+/CD38−/ALDH high population is considered to contain only HSC [21,29,30].…”

Section: Identification Of Leukemic Stem Cellsmentioning

confidence: 99%

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Leukemic stem cells: identification and clinical application

2017

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“…[6][7][8] Higher LPC frequencies and a gene expression profile typical of LPCs at diagnosis are predictive of unfavorable clinical outcomes in AML. [9][10][11][12] Recently, we reported that LPCs in Ph + ALL are enriched in the CD34 + CD38 − CD58 − fraction using an anti-CD122-conditioned NOD/SCID xenograft assay by intra-BM injection. Moreover, our preliminary data indicate that a CD34 + CD38 − CD58 − LPC phenotype at diagnosis is an independent risk factor for relapse in a cohort of 63 patients with de novo Ph + ALL.…”

Section: Introductionmentioning

confidence: 99%

Presence of CD34+CD38−CD58− leukemia-propagating cells at diagnosis identifies patients at high risk of relapse with Ph chromosome-positive ALL after allo-hematopoietic SCT

Kong

et al. 2014

Bone Marrow Transplant

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Relapse of Ph chromosome-positive ALL (Ph + ALL) results from the persistence of leukemia-propagating cells (LPCs). In Ph + ALL, a xenograft assay recently determined that LPCs are enriched in the CD34 + CD38 − CD58 − fraction. Therefore, the prognostic significance of LPCs in Ph + ALL subjects after allogeneic hematopoietic SCT (allo-HSCT) was investigated. A total of 80 consecutive adults with Ph + ALL who underwent allo-HSCT were eligible. A multi-parameter flow cytometry analysis examining CD58-FITC/ CD10-PE/ CD19-APC-Cy7/CD34-PerCP/CD45-Vioblue/ CD38-APC on gated leukemia BM blasts was performed at diagnosis. Based on the original blast phenotypes, subjects were stratified into the CD34 + CD38 − CD58 − group (N = 15) and other phenotype group (N = 65). During minimal residual disease monitoring, significantly higher levels of BCR/ABL transcripts were detected in subjects in the CD34 + CD38 − CD58 − group than in other phenotype group, especially at 3 months post HSCT. In addition, CD34 + CD38 − CD58 − LPCs are directly correlated with a higher 3-year cumulative incidence of relapse (CIR) and worse leukemia-free survival (LFS) and OS. Multivariate analyses indicated that presence of CD34 + CD38 − CD58 − LPCs at diagnosis, and BCR-ABL reduction at 3 months post HSCT were independent risk factors for relapse, LFS and OS. Our data suggest that presence of CD34 + CD38 − CD58 − LPCs at diagnosis allows rapid identification of high-risk patients for relapse after allo-HSCT.

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A clinically relevant population of leukemic CD34+CD38− cells in acute myeloid leukemia

Abstract: Relapse of acute myeloid leukemia (AML

Cited by 197 publications

References 37 publications

Targeted therapy aimed at cancer stem cells: Wilms’ tumor as an example

Targeted therapy aimed at cancer stem cells: Wilms’ tumor as an example

Leukemic stem cells: identification and clinical application

Presence of CD34+CD38−CD58− leukemia-propagating cells at diagnosis identifies patients at high risk of relapse with Ph chromosome-positive ALL after allo-hematopoietic SCT

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