PMID- 19819294
OWN - NLM
STAT- MEDLINE
DCOM- 20100106
LR  - 20091116
IS  - 1873-2399 (Electronic)
IS  - 0301-472X (Linking)
VI  - 37
IP  - 12
DP  - 2009 Dec
TI  - Aldehyde dehydrogenase activity among primary leukemia cells is associated with 
      stem cell features and correlates with adverse clinical outcomes.
PG  - 1423-34
LID - 10.1016/j.exphem.2009.10.001 [doi]
AB  - OBJECTIVE: Animal models have provided evidence for the existence of leukemia 
      stem cells (LSC). However, prospective isolation of human LSC from patients with 
      acute myeloid leukemia (AML), as well as the assessment of their clinical 
      significance, has remained a major challenge. MATERIALS AND METHODS: We have 
      studied the functional characteristics of a subset of leukemia cells that 
      expressed CD34 and high aldehyde dehydrogenase activity (ALDH(br)), which was 
      freshly isolated from the mononuclear cells at the time of diagnosis from the 
      marrow of 68 consecutive patients suffering from AML. RESULTS: The percentage of 
      ALDH(br) cells ranged from 0.01% to 16.0% with a median of 0.5%. Compared to 
      their counterparts with low aldehyde dehydrogenase activity from the same 
      individual patients, the ALDH(br) population showed a significantly higher 
      affinity to human mesenchymal stromal cells (n=12; p<0.01), a more than twofold 
      higher proportion of slow-dividing and quiescent cells (n=4; p<0.05), higher 
      numbers of long-term culture-initiating cell colonies in vitro (n=25; p<0.01), 
      and an enhanced engraftment in the nonobese diabetic/severe combined 
      immunodeficient mouse model (n=3; p<0.05). Above all, we found that the frequency 
      of ALDH(br) cells correlated significantly with diminished survival probability 
      (p=0.025) and with adverse cytogenetic factors (p<0.05). CONCLUSION: A small 
      proportion of leukemia cells derived from the marrow of patients with AML were 
      ALDH(br) and CD34(+). They demonstrated functional characteristics of LSC and 
      high percentages of these cells among the leukemia cells correlated significantly 
      with poor clinical outcome.
FAU - Ran, Dan
AU  - Ran D
AD  - Department of Internal Medicine V, University of Heidelberg, Heidelberg 69120, 
      Germany.
FAU - Schubert, Mario
AU  - Schubert M
FAU - Pietsch, Larissa
AU  - Pietsch L
FAU - Taubert, Isabel
AU  - Taubert I
FAU - Wuchter, Patrick
AU  - Wuchter P
FAU - Eckstein, Volker
AU  - Eckstein V
FAU - Bruckner, Thomas
AU  - Bruckner T
FAU - Zoeller, Margot
AU  - Zoeller M
FAU - Ho, Anthony D
AU  - Ho AD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091009
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (Antigens, CD34)
RN  - EC 1.2.1.3 (Aldehyde Dehydrogenase)
SB  - IM
MH  - Acute Disease
MH  - Adult
MH  - Aged
MH  - Aldehyde Dehydrogenase/genetics/*metabolism
MH  - Animals
MH  - Antigens, CD34/metabolism
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Leukemia, Experimental/enzymology/pathology
MH  - Leukemia, Myeloid/blood/*enzymology/pathology
MH  - Male
MH  - Mesoderm/pathology
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Middle Aged
MH  - Neoplastic Stem Cells/*enzymology/pathology
MH  - Prognosis
MH  - Stromal Cells/enzymology/pathology
MH  - Survival Analysis
MH  - Transplantation, Heterologous
MH  - Tumor Cells, Cultured
MH  - Young Adult
EDAT- 2009/10/13 06:00
MHDA- 2010/01/07 06:00
CRDT- 2009/10/13 06:00
PHST- 2009/08/10 00:00 [received]
PHST- 2009/10/05 00:00 [revised]
PHST- 2009/10/05 00:00 [accepted]
PHST- 2009/10/13 06:00 [entrez]
PHST- 2009/10/13 06:00 [pubmed]
PHST- 2010/01/07 06:00 [medline]
AID - S0301-472X(09)00390-7 [pii]
AID - 10.1016/j.exphem.2009.10.001 [doi]
PST - ppublish
SO  - Exp Hematol. 2009 Dec;37(12):1423-34. doi: 10.1016/j.exphem.2009.10.001. Epub 
      2009 Oct 9.