Bone Marrow Molecule in Elimination of CML Stem Cells
Posted: Tuesday, November 5, 2019
The persistence of chronic myeloid leukemia (CML) stem cells during and after treatment with tyrosine kinase inhibitors prevents cure and requires indefinite therapy. Pleiotrophin—a molecule produced by bone marrow that supports normal blood stem cell growth and recovery from stress—may play a role in perpetuating the growth and survival of CML stem cells, according to a study published in The Journal of Clinical Investigation. John P. Chute, MD, of the University of California, Los Angeles (UCLA), and colleagues suggest that targeting the inhibition of pleiotrophin may help to eradicate cancerous stem cells.
To determine the effect of pleiotrophin on CML stem cells, the research team studied mice with the CML-causing fusion gene and isolated human CML stem cells. The investigators expected mice with the CML-causing fusion gene to quickly develop symptoms and live about 3 to 4 months; however, mice without pleiotrophin had normal white blood cell counts and lived twice as long. When cancerous stem cells were transplanted from mice lacking pleiotrophin into previously healthy mice, the transplant recipients showed little evidence of disease.
When isolated human CML stem cells were analyzed, the cancerous cells had 100 times the levels of pleiotrophin as healthy blood stem cells. The CML stem cells produced their own pleiotrophin in addition to reacting to naturally occurring pleiotrophin. When an antipleiotrophin antibody was added to isolated cells, the cancerous stem cells began to die. Blocking pleiotrophin using antibodies may eliminate the proliferation of cancerous stem cells in patients with CML.
“Our results suggest that it may be possible to eradicate CML stem cells by combining this new targeted therapy with a tyrosine kinase inhibitor,” stated Dr. Chute in a UCLA press release. “This could lead to a day down the road when people with CML may not need to take a tyrosine kinase inhibitor for the rest of their lives.”
Disclosure: For full disclosures of the study authors, visit jci.org.