Characterisation of the Leukemic Stem Cell in a Murine Model of CALM/AF10 Positive Myeloid Leukemia

We have demonstrated, that an acute leukemia with a predominantly
myeloid phenotype can be propagated by a progenitor with lymphoid
characteristics in a mouse model of the t(10;11) (p13;q14)
translocation. Mice transplanted with bone marrow retrovirally
engineered to express the leukemia specific CALM/AF10 fusion gene
consistently developed an acute leukemia with a short latency. The
leukemia showed characteristic myeloid features such as the
presence of myeloid marker positive cells infiltrating multiple
hematopoietic and non-hematopoietic organs, the positivity of
blasts for myeloid specific histochemical stainings and the
depletion of the lymphoid compartment in lymphoid organs. Apart
from the major population of cells expressing myeloid but not
lymphoid markers (M population), a smaller population of cells
expressing myeloid markers as well as the lymphoid marker B220 (
B/M population) and a smaller population expressing only the B220
marker (B population) could be detected in all mice. We determined
that the frequency of leukemia propagating cells was the highest in
the B population and that this population could give rise to the
other two populations of cells, namely the B/M and the M
populations. This indicated that the leukemic stem cell candidate
for the myeloid leukemia in this model of CALM/AF10 induced
transformation is a B220 + cell. Further characterization of these
candidate LSCs revealed the presence of D-JH rearrangements and the
absence of Pax5 transcription. These cells were characterised as
being CD43 + /AA4.1 + /HSA low-pos/CD19 -/FLT3R + /IL-7R low-neg
c-kit low-neg and expressing the early B cell factor (EBF)
transcripts as well as transcripts for the myeloperoxidase (MPO)
gene,bearing a resemblance to Pax5 knockout preBI cells. These
findings indicate that the leukemia-propagating cell in a subset of
acute myeloid leukemias could be a cell with lymphoid
characteristics. The fact that this progenitor cell expressed
markers different from those expressed by the bulk leukemic
population but could still propagate the leukemia raises the
interesting possibility of selectively targeting these cells using
novel therapeutic strategies that aim to eliminate these LSCs.