Stopping Leukemia’s regeneration and preventing relapse

Photo Credits: Eric V. Grave / Photo Researchers, Inc., ISM/Phototake

Many cancers, and leukemia specifically, are difficult to manage because of the chance of relapse if even a tiny cancerous cell is left behind once treatment stops. Therefore, a hot topic in cancer research is the prevention of cancerous regrowth and metastasis. The ADAR1 enzyme has just been identified as a potential target to block relapse of chronic myeloid leukemia by a team bellwethered by researchers of the University of California, San Diego School of Medicine.

Chronic myeloid leukemia (CML) is a cancer of the white blood cells in which the blood forming tissue of the bone marrow (myeloid tissue) proliferates out of control and causes anemia, easy bruising, decreased ability to fend off infection, fever, and joint pain. To combat this, constant intake of tyrosine kinase inhibitors (TKIs) via chemotherapy is necessary. This works to starve the bulk of the tumor of its energy (ATP) and allow the cells to die. This method is usually long term because the TKIs do not always catch every cancerous cell. Relapse is imminent if treatment stops.

For this reason scientists looked to ADAR1.

This enzyme is expressed during very early development of the fetus to promote blood cell proliferation and protect hematopoietic stem cells from viral attack. Leukemic tumors sequester this enzyme for the protection of their own cells activating ADAR1 when it is not needed. This protects the cancerous white blood cells from chemotherapy and allows for enhanced proliferation of the cells.

Researchers performed a 50% knockdown of ADAR1 in vivo using a murine model to test the effects on CML progenitor cells. The self-renewal rate of the leukemia stem cells was reduced by about 30% by this ADAR1 knockdown test. This confirmed the enzyme’s role in the self renewal of the CML cells.

This puts ADAR1 on the table as a potential drug target for cancer treatment. ADAR1 knockdown in patients receiving tyrosine kinase inhibitors may be what is needed to  kill myeloid leukemia tumors, stop its regeneration, and eradicate the disease from the body for good without the need for perpetual treatment.

Combination treatments get another thumbs up from me if we see this therapy in the clinic soon.

Qingfei Jiang, Leslie A. Crews, Christian L. Barrett, Hye-Jung Chun, Angela C. Court,
Jane M. Isquith, Maria A. Zipeto, Daniel J. Goff, Mark Minden, Anil Sadarangani,
Jessica M. Rusert, Kim-Hien T. Dao, Sheldon R. Morris, Lawrence S. B. Goldstein, Marco A. Marra, Kelly A. Frazer, Catriona H. M. Jamieson. ADAR1 promotes malignant progenitor reprogramming
in chronic myeloid leukemia. PNAS, 2012.