Having Blood Cancer for a Long Time may Make It More Aggressive

A type of chronic blood cancer can simmer for many years. Some patients may need treatment to manage this type of blood cancer called myeloproliferative neoplasms (MPN) while others may go through long periods of watchful waiting. But for a small percentage of patients, the slower-paced disease can transform into aggressive cancer, called secondary acute myeloid leukemia, that has few effective treatment options. Little has been known about how this transformation takes place.

But now, researchers at Washington University School of Medicine in St. Louis have identified an important transition point in the shift from chronic to aggressive leukemia.

They have shown that blocking a key molecule in the transition pathway prevents this dangerous disease progression in mice with models of the disease and mice with tumors sampled from human patients. The research appears in the journal Nature Cancer.

Almost every patient who develops acute leukemia after a history of myeloproliferative neoplasms will die from the disease. Therefore, a major focus of our research is to better understand this conversion from chronic to aggressive disease and to develop better therapies and, hopefully, prevention strategies for these patients.

Preventing Slow-Growing Type of Blood Cancer Progressing to Aggressive Form

The study suggests that inhibiting this key transition molecule — called DUSP6 — helps overcome the resistance that these cancers often develop to JAK2 inhibitors, the therapy typically used to treat them. JAK2 inhibitors are an anti-inflammatory therapy also used to treat rheumatoid arthritis.

Since the drug that inhibits DUSP6 is not available for human clinical trials, researchers are interested in exploring treatments that inhibit another molecule that they found is activated downstream of DUSP6 and which they showed is also required to perpetuate the negative effects of DUSP6.

There are drugs in clinical trials that inhibit this downstream molecule, known as RSK1. Oh’s (who is Oh?) team is interested in investigating these drugs for their potential to block the dangerous transition from chronic to aggressive disease and address resistance to JAK2 inhibition.

Advertisement

A future clinical trial might enroll myeloproliferative neoplasm patients who are taking JAK2 inhibitors and, despite that, show evidence of their disease worsening.

At that point, we might add the type of RSK inhibitor that’s now in trials to their therapy to see if that helps block the progression of the disease into an aggressive secondary acute myeloid leukemia.

Advertisement

A newly developed RKS inhibitor is in phase 1 clinical trials for patients with breast cancer, so researchers are hopeful that the work will provide promising foundation for developing a new treatment strategy for patients with this chronic blood cancer.



Source-Eurekalert