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Acute Leukemias

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

Leukemia volume 21, pages 1423–1430 (2007)Cite this article

Abstract

Aldehyde dehydrogenase (ALDH) activity is used to define normal hematopoietic stem cell (HSC), but its link to leukemic stem cells (LSC) in acute myeloid leukemia (AML) is currently unknown. We hypothesize that ALDH activity in AML might be correlated with the presence of LSC. Fifty-eight bone marrow (BM) samples were collected from AML (n=43), acute lymphoblastic leukemia (ALL) (n=8) and normal cases (n=7). In 14 AML cases, a high SSCloALDHbr cell population was identified (ALDH+AML) (median: 14.89%, range: 5.65–48.01%), with the majority of the SSCloALDHbr cells coexpressing CD34+. In another 29 cases, there was undetectable (n=23) or rare (⩽5%) (n=6) SSCloALDHbr population (ALDH−AML). Among other clinicopathologic variables, ALDH+AML was significantly associated with adverse cytogenetic abnormalities. CD34+ BM cells from ALDH+AML engrafted significantly better in NOD/SCID mice (ALDH+AML: injected bone 21.11±9.07%; uninjected bone 1.52±0.75% vs ALDH−AML: injected bone 1.77±1.66% (P=0.05); uninjected bone 0.23±0.23% (P=0.03)) with the engrafting cells showing molecular and cytogenetic aberrations identical to the original clones. Normal BM contained a small SSCloALDHbr population (median: 2.92%, range: 0.92–5.79%), but none of the ALL cases showed this fraction. In conclusion, SSCloALDHbr cells in ALDH+AML might denote primitive LSC and confer an inferior prognosis in patients.

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Acknowledgements

This work was supported by RGC grant (HKU 7548/05M) and a seed Funding Programme for basic research (HKU) to RL.

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Authors and Affiliations

  1. Department of Medicine, The University of Hong Kong, Hong Kong, China

    A M S Cheung, J C K Leung, L Y Y Chan, H Huang, Y L Kwong, R Liang & A Y H Leung

  2. Department of Pathology, The University of Hong Kong, Hong Kong, China

    T S K Wan

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  1. A M S Cheung
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  2. T S K Wan
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Correspondence to A Y H Leung.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Cheung, A., Wan, T., Leung, J. et al. Aldehyde dehydrogenase activity in leukemic blasts defines a subgroup of acute myeloid leukemia with adverse prognosis and superior NOD/SCID engrafting potential. Leukemia 21, 1423–1430 (2007). https://doi.org/10.1038/sj.leu.2404721

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