RE: interferon and dormant cells

[Guest guest]

Giora,

I'm glad that there is finally some research on this. I have not had time to

read the article, but I did this combo for almost l 1/2 years with Dr. Mauro. I

started on INF and Ara-c ( before Gleevec), then went to gleevec alone, and then

the combo. I have now been on Gleevec alone for about 4 1/2 years. Dr. Mauro

still says that I will never come off Gleevec even though I have tested

undetectable for about 4 years now.

AsianCMLSupportGroup ; Sandr1ne@...;

jan@...; CMLHopegooglegroups; ;

anjana@...: giora1@...: Thu, 12 Jun 2008 18:31:08

+0200Subject: [ ] interferon and dormant cells

AuthorEssers, Marieke, ISREC, School of life sciences, EPFL, Epalinges,

Switzerland (P) hello friendsi 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 regardsgioraIFN-?

PROMOTES PROLIFERATION OF DORMANT HSCS IN VIVO, MAKING THEM SUSCEPTIBLE TO

ELIMINATION BY CHEMOTHERAPY Co-author(s) Offner, , ISREC, School of Life

Sciences, Ecole Polytechnique F?d?rale de Lausanne (EPFL), Epalinges,

SwitzerlandBlanco-Bose, , ISREC, School of Life Sciences, Ecole

Polytechnique F?d?rale de Lausanne (EPFL), Epalinges, SwitzerlandWaibler, Zoe,

Ehrlich Institute, Langen, GermanyKalinke, Ulrich, Ehrlich Institute,

Langen, GermanyDuchosal, Michel, Centre Hospitalier Universitaire Vaudois,

Lausanne, SwitzerlandTrumpp, s, ISREC, School of Life Sciences, Ecole

Polytechnique F?d?rale de Lausanne (EPFL), Epalinges, SwitzerlandTopic1.

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. [Non-text portions of

this message have been removed]

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