V. Maguersatta et al., BCR-ABL EXPRESSION IN DIFFERENT SUBPOPULATIONS OF FUNCTIONALLY CHARACTERIZED PH(-LEUKEMIA() CD34(+) CELLS FROM PATIENTS WITH CHRONIC MYELOID), Blood, 88(5), 1996, pp. 1796-1804
In patients with chronic myeloid leukemia (CML), the leukemic (BCR-ABL
(+)/Ph(+)) clone typically includes cells belonging to all of the myel
oid lineages and frequently some B cells. From such observations it ha
s been inferred that the initial BCR-ABL gene rearrangement event occu
rs in a pluripotent hematopoietic stem cell and that the clone subsequ
ently generated is maintained by a subpopulation of neoplastic, BCR-AB
L-expressing cells that retain at least some of the defining propertie
s of normal hematopoietic stem cells. To test this hypothesis directly
, we isolated various subpopulations of CD34(+) cells from fresh or cr
yopreserved samples of peripheral blood from 5 CML patients with high
white blood cell counts, 4 of which were selected because of their exc
lusive content of Ph(+) progenitors (both colony-forming cells and lon
g-term culture-initiating cells [LTC-IC]). Cells in each of the CD34() subpopulations isolated were examined for the presence of BCR-ABL mR
NA using a reverse transcriptase-polymerase chain reaction technique t
hat reproducibly gave a positive signal from single K562 cells. BCR-AB
L mRNA was detected in 117 of 147 samples (80%) in which actin mRNA wa
s demonstrable. This included 60% to 90% of a large number of individu
ally analyzed CD34(+) cells including 46 single CD34(+)CD71(-)CD38(-)
cells and 27 single CD34(+)CD71(+)CD38(+) cells from 3 patients. In 2
of these cases, the same populations also contained a very high freque
ncy of Ph(+) LTC-IC. Our findings demonstrate BCR-ABL gene expression
in neoplastic cells with functional as well as surface marker characte
ristics of very primitive normal hematopoietic cells. This implicates
the BCR-ABL gene product directly in the acquisition by these cells of
properties that alter their interactions with the microenvironment an
d deregulate their proliferation control. (C) 1996 by The American Soc
iety of Hematology.