I am about to formulate a hypothesis and I would appreciate any help
on the validity of what I am proposing. Previous research in
hematopoietic progenitors shows that untransformed early progenitors
reside in hypoxic anatomical niches in the bone marrow. In myeloid
leukemias undifferentiated blast cells enter circulation but apperently
are not effected by the relative high oxygen levels in peripheral
circulation as compared to the environment in which these
undifferentiated cells would reside if they were not leukemic. Thus it
appears the leukemic progenitors have some sort of antioxidant protection
system which allows them to circulate peripherally. Besides the fact
that chronic myeloid leukemia (CML) cells have overexpressed bcl-2 as a
result of the oncoprotein p210, is it possible that the systemic IL-1
levels found in blast crisis of CML patients contribute to the ability of
these early leukemic progenitor cells to circulate peripherally without
apoptosing? It has previously been shown that IL-1 induces
overexpression of oxidant scavenging enzymes such as Mn Superoxide
Dismutase in hematopoietic cells.
The other alternative to why the leukemic cells enter circulation
could be that in leukemic patients there is low oxygen levels due in part
to erythrocyte defects. Is there such conditions documented?
The implications of oxidation induced apoptosis in peripherally
circulating leukemia cells could have valueable treatment implications.
