Enhancement of Myeloproliferative Stem Cells

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earfool
Posts: 13
Joined: Mon Mar 21, 2016 12:18 am

Enhancement of Myeloproliferative Stem Cells

Post by earfool » Sun Apr 26, 2020 6:32 pm

---Jakafi Paradox-- the Sequel
**Enhancement** of Myeloproliferative Stem Cells

(Enhancement) - the process of making something greater… normally we think of enhancement as a good thing… but significantly enhancing cancer *stem* cells that enable cancer cells to grow back with often a vexing resistance to the previously used therapy is NOT a good thing.

Anti-cancer therapies are evaluated based on their ability to reduce myeloproliferative neoplasms, but if the therapies are not killing the cancer stem cells, the tumor will soon grow back (often with a vexing resistance to the previously used therapy)

The stem cell theory of cancer proposes that among all cancerous cells, a few act as stem cells that reproduce themselves and sustain the cancer …if the few are potentiated into the many this prior subpopulation of cells now becomes the driving force of carcinogenesis. (Jakafi Failure Syndrome perhaps.)

A brand new research paper by J Dahlstrom et al 2020… states that JAK2 inhibitors are non-curative and that that JAK2 inhibitors don’t eradicate MPN stem cells. They then determined the effect of the specific JAK inhibitor (LY2784544) on leukemic **stem** (CD34+) cells. They found that there was TRANSIENT an then a rapid recovery of stem cells, in only One week. The JAK inhibitor (named. LY2784544) significantly enhanced the expression of the cancer stem cell factor. (named KLF4}

Paradoxically (excuse the PUN) the also report that Imetelstat would negate this JaK stem cell enhancing effect.

Their conclusions: JAK2 inhibitors thus cause ***enrichment** of LSCs (Leukemic stem cells) and are unlikely to cure MPN as a monotherapy. They also recommend that Simultaneously targeting (inhibiting) JAK2 (Jakafi does this) and Telomerase (Imetelstat does this) should be of significance. (Strange Bedfellows sometimes are the Best)

Here is the reference….

Stay safe and healthy……………………earfool

JAK2 inhibition in JAK2V617F-bearing leukemia cells ***enriches CD34+ leukemic stem cells** that are abolished by the telomerase inhibitor GRN163L
J Dahlström, C Xia, X Xing, X Yuan, M Björkholm, D Xu - Biochemical and Biophysical …, 2020

biopearl123
Posts: 1665
Joined: Fri Jul 20, 2018 5:13 pm

Re: Enhancement of Myeloproliferative Stem Cells

Post by biopearl123 » Sun Apr 26, 2020 6:45 pm

GREAT post earfool, thank you. This may explain the findings presented in the Hu poster at last year's ASH. bp

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