New article: 'Imetelstat differentially affects normal and malignant megakaryopoiesis'

[biopearl]

The following was published on pub med and noted by muttster on YMB:

Imetelstat, a telomerase inhibitor, differentially affects normal and malignant megakaryopoiesis. Pub med

Mosoyan G1, Kraus T2, Ye F3, Eng K4, Crispino JD5, Hoffman R1, Iancu-Rubin C1.

The importance of imetelstat suppressing fibrogenic growth factors is noted. bp

[Fishermangents]

Bio, thanks for posting. Here the full abstract:

Imetelstat, a telomerase inhibitor, differentially affects normal and malignant megakaryopoiesis.
"Imetelstat (GRN163L) is a specific telomerase inhibitor which has demonstrated clinical activity in patients with myeloproliferative neoplasms (MPN) and in patients with solid tumors. The antitumor effects were associated with the development of thrombocytopenia, one of the common side effects observed in patients treated with imetelstat. The events underlying these adverse effects are not apparent. In this report we investigated the potential mechanisms that account for imetelstat's beneficial effects in MPN patients and the manner by which imetelstat treatment leads to a reduction in platelet numbers. Using a well-established system of ex vivo megakaryopoiesis, we demonstrated that imetelestat treatment affects normal megakaryocyte (MK) development by exclusively delaying maturation of MK precursor cells. By contrast, additional stages along MPN MK development were affected by imetelstat resulting in reduced numbers of assayable colony-forming unit (CFU)-MK and impaired MK maturation. In addition, treatment with imetelstat inhibited the secretion of fibrogenic growth factors by malignant but not by normal MK. Our results indicate that the delay observed in normal MK maturation may account for imetelstat-induced thrombocytopenia, while the more global effects of imetelstat on several stages along the hierarchy of MPN megakaryopoiesis may be responsible for the favorable clinical outcomes reported in MPN patients."

Leukemia accepted article preview online, 08 March 2017. doi:10.1038/leu.2017.78.
Link: https://www.ncbi.nlm.nih.gov/pubmed/28270692

[Fishermangents]

bio, I believe you were not impressed by this article. Why is that? The suppressing of fibrogenic growth factors sounds pretty relevant, as it is a very nasty feature of the disease. It also a kind of confirms that imetelstat may reverse fibrosis or prevent it from occurring in the first place. Or am I too optimistic now?

[biopearl]

Fish, I was plenty impressed. The academic institution of origin is strong and the reaffirmation of suppression of fibrogenic
Growth factors renews hope in the MF study outcome. I
I think the ongoing Q2 review of patients with an
otherwise expected median LE of seven months
Speaks volumes. Did not intend to impart a
Leukwarm tone. Regards, bp

[biopearl]

I see now the "what's it it worth" quote that was not mine
and copied over when I took the original post to
Repost here. Sorry for the confusion bp