Researchers continue to build on success of treating AML patients with an alkaloid (HHT) derived from a conifer tree.
Acute myeloid leukemia (AML) is not one disease but a group of hematopoietic neoplasms with varying genotypes, yet similar phenotypes. The cancer arises from hematopoietic stem cells that normally differentiate into myeloid cells such as granulocytes, monocytes, and erythrocytes.
In AML, hematopoietic stem cells proliferate without the ability to differentiate into mature cells. There is an increase in the immature cells and reduction of the needed mature cells, leading to anemia, increased risk of infection, and abnormal bleeding.
AML remains difficult to treat due to the genetic heterogeneity of the disease. A good approach to developing a more successful treatment involves first identifying and targeting important pathway(s) shared by all or most AML subtypes. Results of studies published this year in Haematologica showed that homoharringtonine (HHT), an alkaloid found in the Hainan plum yew found in China (Cephalotaxus hainanensis), can target an essential pathway associated with the development of AML.
HTT is already approved by the US Food and Drug Administration to treat chronic myeloid leukemia that is resistant to tyrosine kinase inhibitors. The recently published HTT research results reveal that it binds to the SP1 transcription factor. The binding of HTT to SP1 affects pathways that are associated with hematopoietic stem cell proliferation and inhibited differentiation.
The main factors involved in the pathways affected by HTT are TET1, a dioxygenase, and FLT3, tyrosine kinase receptor. Mutations and overexpression of FLT3 occur in a large percentage of AML cases. Given these findings, HHT may be a promising treatment for many or most AML cases. Genetic testing can help identify the patients who will most benefit from an HHT treatment approach.
Additional studies are needed to understand the potential for adverse effects as SP1 is expressed in many other tissues. It is also important to elucidate if HHT binds to other important cellular components and what effects those may have.
Overall, the findings regarding HHT is a positive step toward finding a treatment that may benefit a wider population of people with AML.
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Bohlander, S. (2020). A new kid on the block for acute myeloid leukemia treatment? Homoharringtonine interferes with key pathways in acute myeloid leukemia cells. Haematologica, 105(1), 7-9. doi: 10.3324/haematol.2019.234880