Direct demonstration of elevated aldehyde dehydrogenase in human hematopoietic progenitor cells

Abstract

Relative levels of cytoplasmic aldehyde dehydrogenase (ALDH) were determined in selected subpopulations of normal human bone marrow cells using a flow cytometric assay that simultaneously detects a cell surface antigen (as a marker of cell lineage and developmental stage) and the level of ALDH. The intracellular level of this enzyme has been shown to be directly related to cellular resistance to activated cyclophosphamide and is believed to be important in the survival of cells capable of repopulating marrow in autologous bone marrow transplant procedures. Western blot analysis and flow cytometric analysis of four murine cell lines with known ALDH levels were used to establish the relation between ALDH content and fluorescence with an affinity-purified anti-mouse ALDH antibody. An affinity purified anti- human ALDH antibody, characterized by immunoblotting of cytosolic extracts of cell lines with known ALDH content, was used to determine relative ALDH levels in the marrow subpopulations. We found that hematopoietic progenitor cells express the highest level of ALDH, while lymphocytes express the lowest level. Immature erythroid cells express ALDH at a level intermediate between progenitor cells and lymphocytes.

Cancer stem cells in lung cancer: Evidence and controversies

“…ALDH activity forms the basis of a fluorescence‐activated cell sorter‐based assay. Initially used to sort haematopoietic stem cells, a BIODIPY‐aminoacetaldehyde substrate is oxidized intracellularly by ALDH, causing cells to become highly fluorescent. ALDH contributes to drug resistance through detoxification of many cytotoxic agents and has been reported as a reliable CSC marker in several tumour types …”

Cancer stem cell marker ALDH1 expression is associated with lymph node metastasis and poor survival in esophageal squamous cell carcinoma: a study from high incidence area of northern China

“…Aldehyde dehydrogenase 1 (ALDH1) is a detoxifying enzyme responsible for oxidizing a variety of intracellular aldehydes to carboxylic acids 10 . It is highly expressed in hematopoietic progenitors where it is linked to retinoid metabolism with a role in early differentiation of stem cells through the oxidization of retinol to retinoic acid 11,12 . Murine and human hematopoietic stem/progenitor cells have been isolated based on their high levels of ALDH1 activity 13,14 .…”

Activity of aldehyde dehydrogenase in B‐cell and plasma cell subsets of monoclonal gammopathy patients and healthy donors

“…Later, higher activity of this enzyme has been described in many types of cancer stem cells, as well as normal stem cells of different tissues . High enzymatic activity of ALDH has been shown to be a characteristic feature of primitive hematopoietic stem and progenitor cells and was reported also in some hematological cancer‐initiating cells, including multiple myeloma (MM) . Multiple myeloma is characterized by clonal expansion of pathological PCs derived from malignantly transformed B‐cell.…”