The Rocky Road from Cancer Stem Cell Discovery to Diagnostic Applicability
Notice bibliographique
Résumé
Acute myeloid leukemia (AML) is the result of malignant transformation of hematopoietic progenitor cells. These altered cells proliferate and lead to the accumulation of AML blasts. Only a minority population of all AML cells are capable of proliferating in vitro and in vivo. This suggests that AML cells are potentially organized in a hierarchy, with only the most primitive of these cells capable of maintaining the leukemic clone. This hypothesis was the basis for identifying the AML initiating cell and the CSC theory that arose from the subsequent studies. As such, CSCs were first identified in AML in 1990's by John Dick's group in Toronto, Canada AML cells that were CD34+CD38-possessed stem cell like characteristics and de novo leukemia repopulating properties in immunocompromised mice While leukemia initiating cells (LSCs) are in the range of 0.00002 to 0.02% of all unsorted mononuclear blood cells, LSCs were in the range of 0.02 to 2% in the CD34+CD38-sorted cells of tested patient samples (sorting resulting in approximate 100-1000 fold enrichment of the CSC population). In further similarity to normal stem cells, CD34+CD38-expression is also a unique identifier for hematopoietic stem cells (HSCs). Since then, other leukemic stem cell (LSC) markers have been identified. In 1997 and Cancer Stem Cells Theories and Practice 336 (CD90) had the CSC phenotype Later that same group added lack of expression of c-kit (CD117) to the list of potential AML CSC markers, as AML cells from patients that were CD34 + c-kit -were enriched for the CSC population In 2000, Jordan et al., identified a cell surface molecule, interleukin-3 receptor alpha chain (CD123) as being uniquely expressed on AML CSCs, but not HSCs Other than the above described cell surface markers used for the isolation of CSCs, "functional markers" have been explored more recently. The functional marker strategy is based on stem cell characteristics, but does not rely on cell surface adhesion molecules for the viable isolation of a specific cell-subset. For example, Stemcell Technologies developed the aldefluor assay for the isolation of live hematopoietic stem cells based on increased expression of a cytoplasmic enzyme, aldehyde dehydrogenase (ALDH) isoform 1A1. ALDH1A1 is one of 19 ALDH isoforms expressed in humans, and it is a critical detoxifying enzyme responsible for oxidizing aldehydes to carboxylic acids While, predominantly expressed in the epithelium of testis, brain, eye, liver, and kidney, ALDH1A1, is also found in high levels in hematopoietic and neural stem cells ALDH1A1 is proposed to play a role in the differentiation of hematopoietic and neural stem cells via the oxidation of retinal to retinoic acid Retinoic acid activates nuclear retinoic acid receptors (RARs) and RARs subsequently regulate the transcription of genes with RAREs (retinoic acid response elements). Furthermore, ALDH1A1 is known to metabolize and detoxify chemotherapeutics like cyclophosphamide Using the aldefluor assay, Cheung et al., were the first to show that it was possible to isolate the LSCs based on the increased ALDH activity The researchers detected a population of ALDH + AML cells in 14 of 43 patient samples. In the remaining 29 samples an ALDH+ population was rare or unidentifiable. The ALDH + AML cells in most cases coexpressed CD34 + (the previously identified marker) and engrafted significantly better than the ALDH -AML cells in immunocompromised mice. As discussed later, ALDH activity would become one of the few markers discovered that has applicability across a wide range of cancers. It can be said that ALDH activity is a universal CSC marker.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».