Dr. s Hochhaus

[Guest guest]

1.. I am sure some of the old timers will recognize the name " Hochhaus " .

2..

3.. Philipps Universität Marburg, Universitätsklinikum Gießen und Marburg

GmbH, Standort Marburg, Marburg, Germany

We appreciate the comments by Pitini et al highlighting the interesting

mechanisms of action of interferon alfa (IFN-a) that supplement the activity of

tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia (CML).

As monotherapy, IFN-a induces heterogeneous responses in CML, with up to 80% of

early chronic-phase patients achieving hematologic remission but only 8% to 30%

achieving complete cytogenetic remission. Although response correlates with Euro

and Sokal risk scores, the molecular basis for heterogeneous responses and

indeed more broadly the mechanism of response to IFN-a remain poorly understood.

Recent evidence suggested that IFN-a may sensitize dormant stem cells to

imatinib-induced apoptosis by inducing their cell cycle entry. This observation,

which was discussed in our report, was made using short courses of high-dose

IFN-a followed by fluorouracil in a non-CML mouse model. Hematopoietic stem

cells (HSCs) respond to IFN-a treatment by the increased phosphorylation of

STAT1 and PKB/Akt, the expression of IFN target genes, and the upregulation of

stem cell antigen-1 (Sca-1). In HSCs lacking the IFN-a/ß receptor, STAT1 and

Sca-1 are insensitive to IFN stimulation. Conversely, HSCs chronically activated

by IFN are rapidly outcompeted in repopulation assays. Whereas chronic

activation of the IFN pathway in HSCs impairs their function, acute IFN

treatment promotes the proliferation of dormant HSCs in vivo. Read more...

http://jco.ascopubs.org/content/28/25/e440.full

FYI,

Lottie Duthu