期刊
LEUKEMIA
卷 21, 期 7, 页码 1423-1430出版社
SPRINGERNATURE
DOI: 10.1038/sj.leu.2404721
关键词
aldehyde dehydrogenase; leukemia stem cells; NOD/SCID mice
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 SSClo ALDH(br) cell population was identified (ALDH(+)AML) (median: 14.89%, range: 5.65-48.01%), with the majority of the SSClo ALDHbr cells coexpressing CD34(+). In another 29 cases, there was undetectable (n = 23) or rare (<= 5%) ( n 6) SSClo ALDH(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 21.11 +/- 79.07%; uninjected bone 1.527 +/- 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 SSClo ALDH(br) population (median: 2.92%, range: 0.92-5.79%), but none of the ALL cases showed this fraction. In conclusion, SSClo ALDH(br) cells in ALDH(+)AML might denote primitive LSC and confer an inferior prognosis in patients.
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