Project Term
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Memorial Sloan Kettering Cancer Center
New York, NY
United States
Project Summary
Myelofibrosis (MF) is a rare blood cancer with few curative options besides allogeneic stem cell transplant, which has high mortality and relapse rates. We will use spatial transcriptomics to map interactions between mutant MF cells and immune cells in bone marrow samples from patients before and after transplant. Our goal is to identify immune mechanisms that control or fail to eliminate mutant clones, potentially leading to better prediction and prevention of post-transplant relapse.
Lay Abstract
Myelofibrosis is a rare and serious blood cancer that causes scarring in the bone marrow, making it difficult to produce healthy blood cells. Most patients have genetic changes (mutations) in their cancer cells that drive the disease. While medications help manage symptoms, the only cure is a stem cell transplant, where the old blood-forming cells (stem cells) are eliminated or suppressed by chemotherapy and replaced by healthy stem cells from a donor. After transplant, the donor's immune system recognizes and eliminates cancer cells—a process critical for cure. Unfortunately, about one-third of patients experience disease relapse after transplant when cancer cells escape immune detection. We do not understand why the immune system successfully eliminates cancer in some patients but fails in others.
Our research aims to answer this by studying bone marrow samples from 20 myelofibrosis patients before and after transplant. We will use a new and unique technique that detects mutated vs normal genes to show exactly where cancer cells and immune cells are physically located in bone marrow tissue. We can also use this technique to identify which cells come from the donor versus the patient and to see what genes cells are turning on (expressing) or off. By analyzing how these things change over the course of transplant between patients who relapse and patients who do not, our study aims to describe 1) how the bone marrow regenerates after transplant, 2) how immune cells organize in space in relation to mutant cells, and 3) what patterns of immune cell organization and gene expression are associated with relapse.
This research could transform how doctors monitor and treat myelofibrosis patients after transplant. If we identify early warning signs of relapse, doctors could intervene sooner with additional treatments. Our findings may help develop new therapies that boost the immune system's ability to eliminate cancer or improve transplant strategies. While focused on myelofibrosis, these insights about immune-cancer cell interactions could benefit patients with other blood cancers. Ultimately, this work represents an important step toward improving survival and reducing relapse after stem cell transplantation for myelofibrosis.
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