Mobilized peripheral blood SSC^loALDH^br cells have the phenotypic and functional properties of primitive haematopoietic cells and their number correlates with engraftment following autologous transplantation

Aldehyde dehydrogenase activity in leukemic blasts defines a subgroup of acute myeloid leukemia with adverse prognosis and superior NOD/SCID engrafting potential

“…[9][10][11][12][13] In this study, we identified a similar but more robust SSC lo ALDH br population in BM samples from 14 out of 43 AML, but none of the eight ALL cases. Although detailed phenotypic characterization of these leukemia was not available, the myeloid lineage of the AML was confirmed by positive myeloperoxidase and/or Sudan black B 18 and sequence analysis of the ALDH promoter has also revealed sites potentially regulated by a number of putative leukemic genes (Supplementary Information).…”

“…11 Furthermore, in mobilized peripheral blood stem cells (PBSC), the side-scatter low ALDH br (SSC lo ALDH br ) cells are highly enriched for human HSC. 13 Furthermore, ALDH correlated positively with the capability of PBSC graft in hematopoietic reconstitution during HSC transplantation (HSCT). 10 The functional role of ALDH was demonstrated recently, in which diethylaminobenzaldehyde (DEAB), a specific inhibitor of ALDH, deregulated human HSC self renewal by interfering with endogenous retinoic acid biosynthesis.…”

“…It is also highly expressed in human and murine hematopoietic stem and progenitor cells. [8][9][10][11][12][13] In particular, CD34 þ ALDH bright (ALDH br ) cells from human umbilical cord blood (UCB) have been shown to contain all the NOD/SCID engrafting cells in the CD34 þ cells. 11 Furthermore, in mobilized peripheral blood stem cells (PBSC), the side-scatter low ALDH br (SSC lo ALDH br ) cells are highly enriched for human HSC.…”

Is it time to revisit our current hematopoietic progenitor cell quantification methods in the clinic?

“…Moreover, the CD34 counts were influenced by storage of PB or BM stem cells at 41C or room temperature, and correlated less with colonyforming unit (CFU) compared with ALDH activity. Continuously 27 Yes CD34À/low 24 1/24000 Unknown Unknown Unknown CD133+ 28 Same as CD34 Same as CD34+ Similar to CD34 Similar to CD34 CD34+133+ 22 Not reported Not reported Yes (month 3) Yes(month 3,6,9) SSC low/ALDH bright 29 increasing use of cryopreserved stem cell products, namely CB or unrelated products that are subject to long transportation hours, favors the need to use either ALDH activity or colony forming assays to measure the remaining stem cell functions in the product infused. Certainly, ALDH activity quantification by flow cytometry can be accomplished reliably and faster than CFU tests.…”

“…Human BM mononuclear cells, sorted on the basis of their low side light scatter (SSC low ) ALDH bright þ , make up 1.2% of all nucleated cells. Fallon et al 29 were the first to analyze the relationship between the levels of ALDH-expressing cell counts in the graft and resulting engraftment. Interestingly, they were able to detect a correlation between engraftment and SSC low ALDH bright þ , but not CD34 þ cell numbers in fresh autologous PBSC transplants.…”