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

They showed that blocking a key molecule in the pathway prevented the progression of this dangerous disease in mouse models of the disease and in mice with tumors taken from human patients. The study appears in the journal Natural Cancer.


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

Preventing Slow-Growing Blood Cancers That Progress to Aggressive Forms

Research shows that inhibiting this key switch molecule, called DUSP6, helps reverse the resistance these cancers often develop to JAK2 inhibitors, the therapy typically used to treat them. JAK2 inhibitors are an anti-inflammatory therapy that is also used to treat rheumatoid arthritis.

Because a drug that inhibits DUSP6 is not available for clinical trials in humans, the researchers are interested in exploring treatments that show that another molecule they found activates downstream of DUSP6 and is also required to perpetuate the negative effects of DUSP6.

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

A future clinical trial may include patients with myeloproliferative neoplasms who are taking JAK2 inhibitors and yet show evidence of worsening of their disease.

At that point, we can add the type of RSK inhibitor currently in trial to their therapy to see if it helps prevent the disease from progressing to aggressive secondary acute myeloid leukemia.

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

Source: Eurekalert

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