PMID- 7542497
OWN - NLM
STAT- MEDLINE
DCOM- 19950829
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 86
IP  - 3
DP  - 1995 Aug 1
TI  - Cytogenetically aberrant cells in the stem cell compartment (CD34+lin-) in acute 
      myeloid leukemia.
PG  - 1139-47
AB  - Leukemia may be viewed as a clonal expansion of blast cells; however, the role of 
      primitive cells and/or stem cells in disease etiology and progression is unclear. 
      We investigated stem cell involvement in leukemia using fluorescence in situ 
      hybridization (FISH), immunofluorescence labeling of hematopoietic 
      subpopulations, and flow cytometric analysis/sorting to discriminate and quantify 
      cytogenetically aberrant stem cells in 12 acute myeloid leukemia (AML) and three 
      myelodysplastic (MDS) specimens. Flow cytometric analysis and sorting were used 
      to discriminate and collect a primitive subpopulation enriched in stem cells 
      expressing CD34+ and lacking CD33 and CD38 (CD34+lin-). A subpopulation 
      containing progenitors and differentiating myeloid cells expressed CD34, CD33, 
      and CD38 (CD34+lin+). Nine specimens contained less than 10% CD34+ cells and, 
      thus, were considered to be CD34- leukemias. Mature lymphoid, myeloid, and 
      erythroid subpopulations were sorted on the basis of antigen-linked 
      immunofluorescence. Cytogenetically aberrant cells in sorted subpopulations were 
      identified using FISH with enumerator probes selected on the basis of diagnosis 
      karyotype. Cytogenetically aberrant CD34+lin- cells were present at frequencies 
      between 9% and 99% in all specimens. CD34+lin- cytogenetically aberrant cells 
      comprised between 0.05% and 11.9% of the marrow/blood specimens. Cytogenetically 
      aberrant CD34+lin+ cells constituted 0.01% tp 56% of the marrow/blood population. 
      These data demonstrate that aberrant cells are present in primitive CD34+ stem 
      cell compartments, even in CD34- leukemias. Stem cell involvement was confirmed 
      further by sorting lymphoid and erythroid subpopulations from eight specimens in 
      which the predominant leukemic population lacked lymphoid/erythroid 
      differentiation markers. In these specimens, as well as in multiple lineages, 
      suggests involvement of a cell(s) with multilineage capabilities. The ability of 
      aberrant CD34+lin- stem cells to contribute to clonal and compartment expansion 
      within immunofluorescently defined subpopulations was evaluated to explore the 
      functional phenotype of aberrant CD34+lin- cells. Analysis of compartment size 
      and aberrant cell frequency suggests that frequency of cytogenetically aberrant 
      stem cells is uncoupled from compartment size. These data suggest that 
      cytogenetically aberrant cells in the primitive compartment show varying 
      abilities to expand primitive compartments. Cytogenetically aberrant CD34+lin- 
      cells precede the blast subpopulation in hierarchical maturation and may in some 
      cases by considered preleukemic, requiring maturation or additional mutations 
      before transformation (eg, compartmental expansion) occurs.
FAU - Mehrotra, B
AU  - Mehrotra B
AD  - Department of Laboratory Medicine, University of California, San Francisco 94103, 
      USA.
FAU - George, T I
AU  - George TI
FAU - Kavanau, K
AU  - Kavanau K
FAU - Avet-Loiseau, H
AU  - Avet-Loiseau H
FAU - Moore, D 2nd
AU  - Moore D 2nd
FAU - Willman, C L
AU  - Willman CL
FAU - Slovak, M L
AU  - Slovak ML
FAU - Atwater, S
AU  - Atwater S
FAU - Head, D R
AU  - Head DR
FAU - Pallavicini, M G
AU  - Pallavicini MG
LA  - eng
GR  - CA 32102/CA/NCI NIH HHS/United States
GR  - CA 33572/CA/NCI NIH HHS/United States
GR  - CA 60417/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, CD34)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (CD33 protein, human)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Sialic Acid Binding Ig-like Lectin 3)
RN  - EC 3.2.2.- (N-Glycosyl Hydrolases)
RN  - EC 3.2.2.5 (ADP-ribosyl Cyclase)
RN  - EC 3.2.2.5 (CD38 protein, human)
RN  - EC 3.2.2.6 (ADP-ribosyl Cyclase 1)
SB  - IM
MH  - ADP-ribosyl Cyclase
MH  - ADP-ribosyl Cyclase 1
MH  - Acute Disease
MH  - Adult
MH  - Aged
MH  - Antigens, CD/analysis
MH  - Antigens, CD34
MH  - Antigens, Differentiation/analysis
MH  - Antigens, Differentiation, Myelomonocytic/analysis
MH  - Chromosome Aberrations/*pathology
MH  - Chromosome Disorders
MH  - Female
MH  - Humans
MH  - Immunophenotyping
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Myeloid/*pathology
MH  - Male
MH  - Membrane Glycoproteins
MH  - Middle Aged
MH  - Myelodysplastic Syndromes/*pathology
MH  - N-Glycosyl Hydrolases/analysis
MH  - Neoplastic Stem Cells/*pathology
MH  - Sialic Acid Binding Ig-like Lectin 3
EDAT- 1995/08/01 00:00
MHDA- 2001/03/28 10:01
CRDT- 1995/08/01 00:00
PHST- 1995/08/01 00:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1995/08/01 00:00 [entrez]
AID - S0006-4971(20)77422-7 [pii]
PST - ppublish
SO  - Blood. 1995 Aug 1;86(3):1139-47.