The Times today (3 September, page 21) comments on research in the USA published in the journal, Nature, with an accompanying Editorial by Tessa Holyoake and David Vetrie of Glasgow University. The Times article says that patients on imatinib were also given pioglitazone, a drug more usually used for diabetes. The reported outcome was that CML "was eliminated in over 50% of patients" but I am not clear whether that means remission or fully free of CML. An abstract of the Nature article is here: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature15248.html... but the full article is chargeable. Does anyone know the significance of this research and how does it compare with Destiny? David
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Hi David,
Thanks for posting the link to this article. Having read the detail in this one- and another one on the BBC website here: http://www.bbc.co.uk/news/health-34127096 - I think it is highly significant research as it talks about understanding and targeting the quiescent stem cell.... the existence of which is the reason most of us do not see a complete eradication of BCR-ABL1 through TKI therapy (and some of us, me included, even through transplantation).
The article certainly refers to CMR which is complete molecular remission, as opposed to the more often seen MR 4.5 and lower now used because the residual disease is still there at some, albeit very low, molecular level.
By using the term CMR indicates to my less than expert mind that they mean they have seen a complete eradication of the malignant stem cell -which is the driver of this disease - so it follows that by using this particular combination of TKI with anti diabetic drugs (glitazones) may well do what TKI mono-therapy cannot do, that is cure CML!
I know that there has been ongoing research for some years into how leukaemia stem cells manage to 'dodge' inhibitor therapy by switching off - becoming quiescent or dormant - particularly by Professor Tessa Holyoke and her team at Glasgow. So if the research group named in this article have actually proved the concept in humans it may prove to be very significant indeed- and for the majority of us who relapse after a complete cessation of TKI therapy, as DESTINY will eventually show, we may be thrown another lifeboat that will get us to the land of cure after all!
By the way... the interim (draft) agenda for this years patient seminar - to be held at Hammersmith Hospital in West London- includes a presentation by Prof. Holyoake on 'What's New' which hopefully will include updates on this kind of research.
Sandy
"Here we show that the residual CML LCS (Leukaemic stem cell) pool can be gradually purged by the glitazones, antidiabetic drugs that are agonists of peroxisome proliferator-activated receptor-γ (PPARγ).
We found that activation of PPARγ by the glitazones decreases expression of STAT5 and its downstream targets HIF2α5 and CITED26, which are key guardians of the quiescence and stemness of CML LSCs.
When pioglitazone was given temporarily to three CML patients in chronic residual disease in spite of continuous treatment with imatinib, all of them achieved sustained CMR, up to 4.7 years after withdrawal of pioglitazone. This suggests that clinically relevant cancer eradication may become a generally attainable goal by combination therapy that erodes the cancer stem cell pool."