How Some Blood Cancers Progress as Diseases: A Study

A type of chronic leukemia, or cancer of the body’s blood-forming tissues, can simmer for years. In a small proportion of patients, the slow-paced disease can transform into a progressive cancer called secondary acute myeloid leukemia, with few effective treatment options. Images for representation. | | Photo credit: Getty Images/iStockphoto

Study shows that by performing experiments in mice, researchers can identify key transition points in the transition from chronic to advanced hematologic cancers, providing new points of intervention to halt disease progression. Did.

Researchers at the University of Washington School of Medicine in the United States have shown that blocking a key molecule called DUSP6 in the migration pathway could prevent the progression of this dangerous disease in tumors sampled from mouse models of the disease and from human patients. shown in both mice withThe research will be published in a journal natural cancer.

A type of chronic leukemia, or cancer of the body’s blood-forming tissues, can simmer for years. Some patients may need treatment to manage this type of blood cancer called myeloproliferative neoplasm (MPN).

However, in a small minority of patients, the slow-paced disease can transform into a progressive cancer called secondary acute myeloid leukemia, and there are few effective treatment options. Little is known about how this change occurs.

“Secondary acute myeloid leukemia has a poor prognosis,” said senior author Stephen T. Oh, M.D., Ph.D., associate professor of medicine and co-director of the Department of Hematology, School of Medicine.

“Almost all patients who develop acute leukemia after a history of myeloproliferative neoplasia will die of this disease. To better understand it, to develop better treatments, and hopefully preventative strategies for these patients,” Oh said.

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This study suggests that inhibiting this key transitional molecule, DUSP6, can help these cancers overcome the resistance they often develop to JAK2 inhibitors, the therapies commonly used to treat them. suggesting.

JAK2 inhibitors are anti-inflammatory therapies also used to treat rheumatoid arthritis.

“These patients are commonly treated with JAK2 inhibitors, but their disease progresses despite that treatment, so we are trying to identify how the disease worsens in the JAK2 inhibitor setting as well.

The researchers delved into the genetics of these tumors, both during the sluggish chronic phase and after the disease transformed into an aggressive form while the patient was taking JAK2 inhibitors.

The DUSP6 gene was strikingly highly expressed in the 40 patients whose tumors were analyzed in this study.

Deletion of the DUSP6 gene using genetic techniques prevented the progression of mice with this model of cancer to progressive disease.

The researchers also tested a drug compound that inhibits DUSP6 and found that the compound (available only in animal studies) was effective in two different mouse models of cancer and in mice with human tumors sampled from patients with chronic disease. found to stop the progression of to progressive disease.

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Lowering DUSP6 levels, both genetically and pharmacologically, also reduced inflammation in these models.

Because drugs that inhibit DUSP6 are not available for human clinical trials, Oh and his colleagues found that DUSP6 is activated downstream and is also required to sustain DUSP6’s negative effects. I am interested in finding therapeutics that inhibit another molecule that has been shown to be. There are drugs in clinical trials that block this downstream molecule known as RSK1.

Oh’s team is interested in investigating these agents for their potential to block the dangerous transition from chronic to progressive disease and to address resistance to JAK2 inhibition, the study said. increase.

“Future clinical trials may enroll patients with myeloproliferative neoplasms who are taking JAK2 inhibitors, but we nonetheless show evidence of worsening disease,” says Oh. said Mr.

“At that point, we may add a type of RSK inhibitor currently being tested to see if it helps stop the progression of the disease to advanced secondary acute myeloid leukemia. there is.

“As a newly developed RKS inhibitor is entering Phase 1 clinical trials in breast cancer patients, our study will help develop new therapeutic strategies for patients with this chronic hematological cancer. We expect it to be a promising foundation,” said Oh.