Scientists Uncover New Treatment for Bone Marrow Cancer

Scientists at MetroHealth and Case Western Reserve University (CWRU) School of Medicine have discovered a potential way to treat myelofibrosis, a rare blood cancer, when standard drugs stop working.

^{Huiqin Bian, PhD, and Shujun Liu, PhD}

The study - led by postdoctoral research fellow Huiqin Bian, PhD, the study's first author; and corresponding author Shujun Liu, PhD, Professor in the Department of Medicine and Cell and the Gene Therapy Institute at MetroHealth and Professor of Medicine at CWRU - has been published in Blood Cancer Journal and funded by the National Cancer Institute.

The research study identifies a specific molecular "communication line" involving NFκB/IL-6/JAK2/STAT signaling pathway in the body that helps the disease survive during and/or post treatment.

In myelofibrosis, scar tissue builds up in the bone marrow, causing the spleen to swell and the body to struggle to make healthy blood cells. Most cases are caused by specific genetic mutations like JAK2. While current JAK2 inhibitor drugs taken orally help patients feel better, they don't cure the disease and often stop working over time. This new research explains why these drugs often fail.

The team discovered a previously hidden "survival axis" in the cancer cells that keeps them growing even when the standard JAK2 inhibitors are active. A specific chain reaction (the NFκB/IL-6/JAK2/STAT pathway) acts as a backup engine for the cancer. By using two other drugs - ixazomib (already used for other blood cancers) or emetine - the researchers were able to "cut the power" to this backup engine. This new approach effectively stopped the disease from growing and bypassed the drug resistance that often limits current treatments.

"This work changes how we think about current treatments and gives us a new perspective on how myelofibrosis works," said Dr. Bian, lead study author. "We were surprised to find that the disease's survival signals can stay active even if patients take JAK2 inhibitors for a short time or on and off. Our research identified a new "growth pathway" that helps the cancer spread, regardless of whether a patient has the most common JAK2 mutation."

The study findings could lead to new clinical trials using ixazomib or emetine, said Dr. Liu. "These drugs might be used on their own or combined with current treatments to overcome the limitations of today's medicine. This approach aims to break through the current barriers in treatment and offer new ways to manage or even prevent myelofibrosis."

The team now plans to test these results in a larger group of patients and start clinical trials.