15 January 2019

A new switch controls leukemia development

Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is a highly aggressive cancer for which survival rates have only improved marginally for the last 4-5 decades, thus emphasizing the need for novel treatment strategies.

In a recent paper, published in Nature Communications, Ying Ge and other members of the Porse group at DanStem/BRIC/Finsen Laboratory, set out to test the importance of so-called splicing factors in the development of Acute Myeloid Leukemia (AML). Splicing factors are important mediators of the correct processing of the cell´s genetic information into protein. “Specifically, we used a functional screening approach to identify RBM25 as a negative regulator of AML”, says the first author, postdoc Ying Ge.

In their work, the team show that inhibiting RBM25 leads to increased expression of an alternative version of BIN1, a known inhibitor of the tumor promoting factor (oncogene) MYC. This alternative version impedes the function of “normal” BIN1 thus leading to increased MYC activity and ultimately to accelerated tumor growth. Furthermore, by scrutinizing publically availably AML datasets, the authors provide clear indications that the characterized mechanism is clinically relevant.

The mechanism by which BM25 regulates AML development.

“Characterizing this novel pathway impinging on a known oncogene have provide important new insights into the mechanisms regulating tumor growth in AML and possibly other cancers”, says Professor Bo Porse. “In particular, our work highlights the need for assessment of alternative protein versions in cancer, as this will not only improve our understanding of cancer but also has the potential for the development of novel treatment strategies”.

See more information about the Porse group

Ge, Y., Schuster, M.B., Pundhir, S., Rapin, N., Bagger, F.O., Sidiropoulos, N., Hashem, N., and Porse, B.T. (2019). The splicing factor RBM25 controls MYC activity in acute myeloid leukemia. Nature Communications 10, doi: 10.1038/s41467-018-08076-y.