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Blood, Vol. 92 No. 12 (December 15), 1998:
pp. 4758-4763
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
Naoto Takahashi,
Ikuo Miura,
Kohki Saitoh, and
Akira B. Miura
From the Third Department of Internal Medicine, Akita University
School of Medicine, Akita, Japan.
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.
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