AuthorEssers, Marieke, ISREC, School of life sciences, EPFL, Epalinges,
Switzerland (P)
hello friends
i just had a long conversation with a good friend, a leading hematologist
in Israel, .
he was very excited about this abstract from eha. this abstract was
elected as one of the best 5 abstracts from the meeting and will be presented
at a presidentail session.
the idea that interferon can get the dormant cells out and than kill them
with another agent, is a posible oppening to what we are all looking for- some
kind of cure for cml.
according to my friend, the timing of using ifn and glivec is important.
he thinks that the best posible treatment for new patients will be 3 months of
glivec alone, to reduce the number of the leukemic cells or burden. than he
will start interferon posibly in combination with imatinib, but it may work
also as a sole agent ending with imatinib to kill the dormant cells that were
proliferated by the ifn. according to him even when you stop the ifn, there are
t-cells that stay in the system and fight the cml cells.
i hope that there will be more trials going this direction. al in all
this is very encouraging.
best regards
giora
IFN-? PROMOTES PROLIFERATION OF DORMANT HSCS IN VIVO, MAKING THEM
SUSCEPTIBLE TO ELIMINATION BY CHEMOTHERAPY
Co-author(s) Offner, Sandra, ISREC, School of Life Sciences, Ecole
Polytechnique F?d?rale de Lausanne (EPFL), Epalinges, Switzerland
Blanco-Bose, William, ISREC, School of Life Sciences, Ecole Polytechnique
F?d?rale de Lausanne (EPFL), Epalinges, Switzerland
Waibler, Zoe, Paul Ehrlich Institute, Langen, Germany
Kalinke, Ulrich, Paul Ehrlich Institute, Langen, Germany
Duchosal, Michel, Centre Hospitalier Universitaire Vaudois, Lausanne,
Switzerland
Trumpp, Andreas, ISREC, School of Life Sciences, Ecole Polytechnique
F?d?rale de Lausanne (EPFL), Epalinges, Switzerland
Topic1. Developmental hematopoiesis and stem cells
KeywordsActivation, Hematopoietic stem cell, Interferon alpha
The life-long maintenance of blood is dependent on the activity of bone
marrow haematopoietic stem cells (HSCs), which are multipotent and display long
term self-renewal capacity. In the mature organism, stem cell activity is
retained in a reservoir of dormant HSCs, which do not significantly contribute
to the daily haematopoiesis. However, upon haematopoietic injury these cells
can be efficiently recruited into the cell cycle actively supporting the
recovery of the haematopoietic system. Up to now, the signals, which promote
the exit of HSCs out of the dormant stage, are largely unknown. Here we show
that HSCs efficiently exit G0 and enter the cell cycle in response to treatment
with interferon-alpha (IFN?) in vivo. IFN? treatment results in the
phosphorylation of STAT1 and PKB/Akt, and expression of IFN? target genes in
HSCs, as well as stem cell antigen (Sca-1) up-regulation at their surface. HSCs
lacking IFNAReceptor, STAT1 or Sca-1 do not show increased proliferation in
response to IFN? stimulation. Priming of HSCs with IFN? followed by treatments
with the anti-proliferative chemotherapeutic agent 5-FU causes lethality due to
HSC exhaustion, indicating that 5-FU resistant dormant HSCs can be sensitized
to this drug by pre-treatment with IFN? in vivo. These results demonstrate a
novel role for IFN? on activation of dormant stem cells in vivo and, since
dormancy is thought to be a typical feature of certain haematological tumour
cells as well, may help to clarify the so far unexplained clinical effects of
IFN? on dormant leukaemic stem cells.
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