PMID- 2105108
OWN - NLM
STAT- MEDLINE
DCOM- 19900314
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 75
IP  - 3
DP  - 1990 Feb 1
TI  - Induction of differentiation in blast cells and leukemia colony-forming cells 
      from patients with acute myeloid leukemia.
PG  - 721-9
AB  - The characteristic lesion in acute myeloid leukemia (AML) is the failure of 
      myeloid cells to differentiate normally, leading to the accumulation of immature 
      blast cells (BC) in the bone marrow. We determined whether BC and leukemia 
      colony-forming cells (L-CFC) from AML patients could differentiate in vitro after 
      short-term culture with interferon-gamma (IFN gamma), 1,25 dihydroxyvitamin D3 
      (D3), retinoic acid (RA), tumor necrosis factor-alpha (TNF alpha), and 
      granulocyte-monocyte colony-stimulating factor (GM-CSF). Expression of myeloid 
      differentiation antigens CD15, CD14, CD33, and p124 was determined on the BC by 
      immunofluorescence and on the L-CFC by monoclonal antibody (MoAb) and complement 
      (C')-mediated cytotoxicity followed by cloning in methylcellulose. We found that 
      26 of 39 (67%) cases demonstrated changes in the expression of myeloid 
      differentiation antigens on the BC, and 6 of 7 (86%) cases showed an altered 
      L-CFC myeloid antigen phenotype after short-term culture with differentiating 
      agents. Alterations in myeloid antigen expression in the L-CFC population 
      correlated with a reduction in L-CFC cloning potential. In the BC, alterations of 
      myeloid differentiation antigens occurred in a manner consistent with those 
      observed during normal myelopoiesis. For example, CD14 antigen expression (a 
      late-stage monocyte antigen) increased on BC from 12 of 39 (31%) cases, and p124 
      (an antigen expressed both by myeloid progenitor cells and by a subset of 
      monocytes) increased on 15 of 39 (38%) cases. Changes in the expression of CD33 
      antigens (expressed normally by myeloid progenitor cells and by mature monocytes) 
      on the BC were variable, with 7 of 29 cases (24%) showing a decrease and 7 of 29 
      cases (24%) showing an increase. When comparisons were made between pairs of 
      differentiation agents that caused the altered expression of an antigen on either 
      the BC or L-CFC of a patient, the majority of changes were in the same direction 
      (either both "increased" or both "decreased"). This suggests that the direction 
      of antigen change is characteristic of the leukemia cell subpopulation for each 
      patient and not of the stimulatory agent. This study demonstrates that cells from 
      more than two thirds of AML cases examined responded to various differentiation 
      agents in vitro as measured by changes in the expression of myeloid 
      cell-associated surface antigens and by alterations in cloning potential of the 
      L-CFC, a finding of potential clinical significance.
FAU - Howell, A L
AU  - Howell AL
AD  - Department of Medicine, Dartmouth Medical School, Hanover, NH 03756.
FAU - Stukel, T A
AU  - Stukel TA
FAU - Bloomfield, C D
AU  - Bloomfield CD
FAU - Davey, F R
AU  - Davey FR
FAU - Ball, E D
AU  - Ball ED
LA  - eng
GR  - CA31888/CA/NCI NIH HHS/United States
GR  - CA37027/CA/NCI NIH HHS/United States
GR  - CA43184/CA/NCI NIH HHS/United States
GR  - etc.
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, Differentiation, Myelomonocytic)
RN  - 0 (Colony-Stimulating Factors)
RN  - 0 (Growth Substances)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 5688UTC01R (Tretinoin)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
MH  - Antigens, CD/*metabolism
MH  - Antigens, Differentiation, Myelomonocytic/*metabolism
MH  - Calcitriol/pharmacology
MH  - Cell Differentiation/*drug effects
MH  - Cell Division/drug effects
MH  - Colony-Stimulating Factors/pharmacology
MH  - Granulocyte-Macrophage Colony-Stimulating Factor
MH  - Growth Substances/pharmacology
MH  - Humans
MH  - Interferon-gamma/pharmacology
MH  - Leukemia, Myeloid, Acute/immunology/*pathology
MH  - Neoplastic Stem Cells/immunology/*pathology
MH  - Tretinoin/pharmacology
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1990/02/01 00:00
MHDA- 1990/02/01 00:01
CRDT- 1990/02/01 00:00
PHST- 1990/02/01 00:00 [pubmed]
PHST- 1990/02/01 00:01 [medline]
PHST- 1990/02/01 00:00 [entrez]
AID - S0006-4971(20)85760-7 [pii]
PST - ppublish
SO  - Blood. 1990 Feb 1;75(3):721-9.