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Aldehyde dehydrogenase 1 gene expression and enzymatic activity are elevated in CoCSC and using an in vitro culture system that maintains CoCSC as demonstrated by serial transplants and lentiviral marking of single cell-derived clones, we further show that ALDH1 enzymatic activity is a major mediator of resistance to cyclophosphamide: a classical chemotherapeutic agent.

Scott J. Dylla et al.

PLoS ONE 3 (6), 18 Jun 2008

Resistance to CPA has been suggested to result from high cytoplasmic aldehyde dehydrogenase (ALDH) enzyme activity: particularly that of ALDH1 and ALDH3 [20] , [21] , which oxidize and inactivate the bioactive metabolic byproduct of CPA, aldophosphamide/4-hydroxycyclophosphamide (4-HC) [22] , [23] .

Scott J. Dylla et al.

PLoS ONE 3 (6), 18 Jun 2008

Cell Stem Cell 1 389 402 18371377 20 Moreb JS Mohuczy D Ostmark B Zucali JR 2007 RNAi-mediated knockdown of aldehyde dehydrogenase class-1A1 and class-3A1 is specific and reveals that each contributes equally to the resistance against 4-hydroperoxycyclophosphamide.

Scott J. Dylla et al.

PLoS ONE 3 (6), 18 Jun 2008

Drug Metab Rev 36 279 299 15237855 24 Sladek NE 1999 Aldehyde dehydrogenase-mediated cellular relative insensitivity to the oxazaphosphorines.

Scott J. Dylla et al.

PLoS ONE 3 (6), 18 Jun 2008

Hum Mol Genet 15 167 187 16339214 27 Hess DA Meyerrose TE Wirthlin L Craft TP Herrbrich PE 2004 Functional characterization of highly purified human hematopoietic repopulating cells isolated according to aldehyde dehydrogenase activity.

Scott J. Dylla et al.

PLoS ONE 3 (6), 18 Jun 2008

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