Leukemia Hypothesis

T Ichim TEICHIM at AHS.watstar.uwaterloo.ca
Tue Mar 19 21:10:06 EST 1996

     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.

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