Killing quiescent cells

[Guest guest]

Roy on the Asian group posted this abstract from Leukemia by Tessa

Holyoake's group, which demonstrates activity of IM combined the FTI

Lornafarnib against quiescent CML cells. Good stuff. I've written to Tessa

to ask whether and when trials might begin. I'll let you know what I hear

Hi to all,

R

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Leukemia. 2005 May 12

Lonafarnib reduces the resistance of primitive quiescent CML cells to

imatinib mesylate in vitro.

nsen HG, Allan EK, Graham SM, Godden JL, Richmond L, Elliott MA,

Mountford JC, Eaves CJ, Holyoake TL.

1ATMU, Section of Experimental Haematology, Department of Medicine

and Haematology, Division of Cancer Sciences & Molecular Pathology,

University of Glasgow, Glasgow, UK.

Recent studies indicate that a rare population of primitive quiescent

BCR-ABL(+) cells are innately insensitive to imatinib mesylate (IM)

and persist after IM therapy of patients with chronic myeloid

leukemia (CML). New approaches to the eradication of these cells are

therefore likely to be crucial to the development of curative

therapies for CML. We have now found that Ara-C, LY294002 (a PI-3

(phosphatidylinositol-3' kinase) kinase inhibitor), 17AAG (a heat-

shock protein (HSP)-90 antagonist) and lonafarnib (a

farnesyltransfease inhibitor) all enhance the toxicity of IM on K562

cells and on the total CD34(+) leukemic cell population from chronic

phase CML patients. However, for quiescent CD34(+) leukemic cells,

this was achieved only by concomitant exposure of the cells to

lonafarnib. Ara-C or LY294002 alone blocked the proliferation of

these cells but did not kill them, and Ara-C, LY294002 or 17AAG in

combination with IM enhanced the cytostatic effect of IM but did not

prevent the subsequent regrowth of the surviving leukemic cells.

These studies demonstrate the importance of in vitro testing of novel

agents on the subset of primary leukemic cells most likely to

determine long-term treatment outcomes in vivo

[Guest guest]

Good stuff, indeed! Thanks for bringing this to , . The Holyoake

Project seems to be coming through in fine form.

All the best,

[ ] Killing quiescent cells

Roy on the Asian group posted this abstract from Leukemia by Tessa

Holyoake's group, which demonstrates activity of IM combined the FTI

Lornafarnib against quiescent CML cells. Good stuff. I've written to Tessa

to ask whether and when trials might begin. I'll let you know what I hear

Hi to all,

R

______________

Leukemia. 2005 May 12

Lonafarnib reduces the resistance of primitive quiescent CML cells to

imatinib mesylate in vitro.

nsen HG, Allan EK, Graham SM, Godden JL, Richmond L, Elliott MA,

Mountford JC, Eaves CJ, Holyoake TL.

1ATMU, Section of Experimental Haematology, Department of Medicine

and Haematology, Division of Cancer Sciences & Molecular Pathology,

University of Glasgow, Glasgow, UK.

Recent studies indicate that a rare population of primitive quiescent

BCR-ABL(+) cells are innately insensitive to imatinib mesylate (IM)

and persist after IM therapy of patients with chronic myeloid

leukemia (CML). New approaches to the eradication of these cells are

therefore likely to be crucial to the development of curative

therapies for CML. We have now found that Ara-C, LY294002 (a PI-3

(phosphatidylinositol-3' kinase) kinase inhibitor), 17AAG (a heat-

shock protein (HSP)-90 antagonist) and lonafarnib (a

farnesyltransfease inhibitor) all enhance the toxicity of IM on K562

cells and on the total CD34(+) leukemic cell population from chronic

phase CML patients. However, for quiescent CD34(+) leukemic cells,

this was achieved only by concomitant exposure of the cells to

lonafarnib. Ara-C or LY294002 alone blocked the proliferation of

these cells but did not kill them, and Ara-C, LY294002 or 17AAG in

combination with IM enhanced the cytostatic effect of IM but did not

prevent the subsequent regrowth of the surviving leukemic cells.

These studies demonstrate the importance of in vitro testing of novel

agents on the subset of primary leukemic cells most likely to

determine long-term treatment outcomes in vivo

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