PMID- 11777957
OWN - NLM
STAT- MEDLINE
DCOM- 20020131
LR  - 20190515
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 168
IP  - 2
DP  - 2002 Jan 15
TI  - The BCR/ABL transgene causes abnormal NK cell differentiation and can be found in 
      circulating NK cells of advanced phase chronic myelogenous leukemia patients.
PG  - 643-50
AB  - NK cells from the blood of chronic myelogenous leukemia (CML) patients are 
      progressively decreased in number as the disease progresses from chronic phase to 
      blast crisis. We hypothesize that BCR/ABL may be directly responsible by 
      interfering with NK cell differentiation. CD34(+)HLA-DR(+) cells from CML 
      patients were studied for their capacity to differentiate into NK cells. The NK 
      cell cloning frequency was significantly decreased from CML CD34(+)HLA-DR(+) 
      cells compared with cells from normal donors, yet CD34(+)HLA-DR(+) cells gave 
      rise to BCR/ABL(+) NK cells in some patients. This finding prompted us to further 
      investigate circulating NK cells from the blood of CML patients. CD56(+)CD3(-) NK 
      cells were sorted from CML patients and examined by fluorescence in situ 
      hybridization (FISH). In contrast to chronic phase CML, significant numbers of NK 
      cells from advanced phase CML patients were BCR/ABL(+), whereas T cells were 
      always BCR/ABL(-) regardless of the disease stage. To test the effects of BCR/ABL 
      as the sole genetic abnormality, BCR/ABL was transduced into umbilical cord blood 
      CD34(+) cells, and NK development was studied. p210-enhanced green fluorescence 
      protein-transduced cells gave rise to significantly decreased numbers of NK cells 
      compared with enhanced green fluorescence protein transduction alone. In 
      addition, the extrinsic addition of BCR/ABL-transduced autologous CD34(+) cells 
      suppressed the NK cell differentiation of normal umbilical cord blood 
      CD34(+)CD38(-) cells. This study provides the first evidence that BCR/ABL is 
      responsible for the altered differentiation of NK cells and that the NK cell 
      lineage can be involved with the malignant clone in advanced stage CML.
FAU - Nakajima, Hikaru
AU  - Nakajima H
AD  - Department of Medicine, University of Minnesota Cancer Center, Minneapolis, MN 
      55455, USA.
FAU - Zhao, Robert
AU  - Zhao R
FAU - Lund, Troy C
AU  - Lund TC
FAU - Ward, Jeanne
AU  - Ward J
FAU - Dolan, Michelle
AU  - Dolan M
FAU - Hirsch, Betsy
AU  - Hirsch B
FAU - Miller, Jeffrey S
AU  - Miller JS
LA  - eng
GR  - M0-1-RR00400/RR/NCRR NIH HHS/United States
GR  - P01-CA-65493/CA/NCI NIH HHS/United States
GR  - R01-HL-55417/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, CD34)
RN  - 0 (Luminescent Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
SB  - IM
MH  - Animals
MH  - Antigens, CD34/biosynthesis
MH  - Blast Crisis/genetics/immunology/pathology
MH  - Cell Differentiation/genetics/immunology
MH  - Cell Line
MH  - Cells, Cultured
MH  - Clone Cells/immunology/pathology
MH  - Female
MH  - Fusion Proteins, bcr-abl/*blood/*genetics/physiology
MH  - Genes, abl/*immunology
MH  - Green Fluorescent Proteins
MH  - Hematopoiesis/genetics/immunology
MH  - Hematopoietic Stem Cells/immunology/pathology
MH  - Humans
MH  - Killer Cells, Natural/immunology/*metabolism/*pathology
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL 
      Positive/blood/*genetics/*immunology/pathology
MH  - Leukocyte Count
MH  - Luminescent Proteins/genetics
MH  - Mice
MH  - Transduction, Genetic
MH  - Transgenes/*immunology
EDAT- 2002/01/05 10:00
MHDA- 2002/02/01 10:01
CRDT- 2002/01/05 10:00
PHST- 2002/01/05 10:00 [pubmed]
PHST- 2002/02/01 10:01 [medline]
PHST- 2002/01/05 10:00 [entrez]
AID - 10.4049/jimmunol.168.2.643 [doi]
PST - ppublish
SO  - J Immunol. 2002 Jan 15;168(2):643-50. doi: 10.4049/jimmunol.168.2.643.