PMID- 9845542
OWN - NLM
STAT- MEDLINE
DCOM- 19990205
LR  - 20211203
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 92
IP  - 12
DP  - 1998 Dec 15
TI  - Lineage involvement of stem cells bearing the philadelphia chromosome in chronic 
      myeloid leukemia in the chronic phase as shown by a combination of 
      fluorescence-activated cell sorting and fluorescence in situ hybridization.
PG  - 4758-63
AB  - Chronic myeloid leukemia (CML) is thought to arise from a pluripotent 
      hematopoietic stem cell that has undergone a reciprocal translocation between the 
      BCR gene on chromosome 22 and the ABL proto-oncogene on chromosome 9. This 
      rearrangement results in a shortened chromosome 22, designated the Philadelphia 
      (Ph) chromosome. The Ph chromosome has been found in cells from all hematopoietic 
      lineages except mature T lymphocytes. To examine this issue, we combined 
      fluorescence-activated cell sorting (FACS) and fluorescence in situ hybridization 
      (FISH) to study lineage involvement of mature cells and stem cells in 12 patients 
      with CML in the chronic phase. We found Ph chromosomes in myeloid cells and most 
      B lymphocytes (CD19(+)) but not in mature T cells (CD3(+)) or natural killer (NK) 
      cells (CD3(-)56(+)). Moreover, evidence of BCR/ABL fusion was found in 
      pluripotent stem cells (CD34(+)Thy-1(+)), B-progenitor cells (CD34(+)CD19(+)), 
      T/NK progenitor cells (CD34(+)CD7(+) cells), and T progenitor cells 
      (CD34(+)CD7(+)CD5(+)) with a frequency equal to that in all CD34(+) cells 
      isolated by FACS from bone marrow cells. T lymphocytes showed a marked decrease 
      in Ph+ cells between progenitor cells and mature cells. Moreover, the ratios of 
      Ph+ to Ph- cells in mature T cells and NK cells were below background levels, 
      whereas Ph+ B lymphocytes also decreased during their maturation. These data 
      suggest that Ph+ lymphocytes are eliminated during differentiation. In contrast 
      to FISH of blood and bone marrow, which gives information principally about 
      mature cells, the technique of "sorter FISH (FACS + FISH)" provides a powerful 
      tool to explore the cytogenetic changes in immature cell populations of stem cell 
      diseases based on immunophenotypes. Further clarification of genetic changes in 
      stem cells could be achieved by using sorter FISH with monoclonal antibodies.
FAU - Takahashi, N
AU  - Takahashi N
AD  - Third Department of Internal Medicine, Akita University School of Medicine, 
      Akita, Japan.
FAU - Miura, I
AU  - Miura I
FAU - Saitoh, K
AU  - Saitoh K
FAU - Miura, A B
AU  - Miura AB
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD34)
RN  - 0 (MAS1 protein, human)
RN  - 0 (Proto-Oncogene Mas)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antigens, CD34/analysis
MH  - B-Lymphocytes/chemistry/ultrastructure
MH  - Bone Marrow Cells/ultrastructure
MH  - Cell Lineage
MH  - Cell Separation
MH  - Female
MH  - Flow Cytometry
MH  - Genes, abl/genetics
MH  - Humans
MH  - Immunophenotyping
MH  - In Situ Hybridization, Fluorescence
MH  - Killer Cells, Natural/chemistry/ultrastructure
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*genetics
MH  - Leukemia, Myeloid, Chronic-Phase/*genetics
MH  - Leukocytes, Mononuclear/ultrastructure
MH  - Lymphocyte Subsets/*ultrastructure
MH  - Male
MH  - Middle Aged
MH  - *Philadelphia Chromosome
MH  - Proto-Oncogene Mas
MH  - Stem Cells/*ultrastructure
MH  - T-Lymphocytes/chemistry/ultrastructure
EDAT- 1998/12/09 00:00
MHDA- 1998/12/09 00:01
CRDT- 1998/12/09 00:00
PHST- 1998/12/09 00:00 [pubmed]
PHST- 1998/12/09 00:01 [medline]
PHST- 1998/12/09 00:00 [entrez]
AID - S0006-4971(20)57703-3 [pii]
PST - ppublish
SO  - Blood. 1998 Dec 15;92(12):4758-63.