1. ¹Department of Medicine, The University of Hong Kong, Hong Kong, China
2. ²Department of Pathology, The University of Hong Kong, Hong Kong, China

Correspondence: Dr AYH Leung, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pok Fu Lam Road, Hong Kong, China. E-mail: ayhleung@hku.hk

Received 22 January 2007; Revised 13 March 2007; Accepted 26 March 2007; Published online 3 May 2007.

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 SSC^loALDH^br cell population was identified (ALDH⁺AML) (median: 14.89%, range: 5.65–48.01%), with the majority of the SSC^loALDH^br cells coexpressing CD34⁺. In another 29 cases, there was undetectable (n=23) or rare (5%) (n=6) SSC^loALDH^br 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 21.119.07%; uninjected bone 1.520.75% vs ALDH^-AML: injected bone 1.771.66% (P=0.05); uninjected bone 0.230.23% (P=0.03)) with the engrafting cells showing molecular and cytogenetic aberrations identical to the original clones. Normal BM contained a small SSC^loALDH^br population (median: 2.92%, range: 0.92–5.79%), but none of the ALL cases showed this fraction. In conclusion, SSC^loALDH^br cells in ALDH⁺AML might denote primitive LSC and confer an inferior prognosis in patients.