Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM )retired), MSEd
The Bottom Line:
The presence of specific precancerous mutations may predispose patients to an increased risk of developing certain side effects in response to therapies.
Who Performed the Research and Where Was it Presented:
Dr. Paolo Ghia from Università Vita-Salute San Raffaele in Milano, Italy, and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2024.
Background:
As people age, they accumulate mutations in their DNA. Most of the time, these mutations have no functional consequence, but occasionally, a mutation can confer a survival advantage to a cell. These cells replicate and produce more cells with the same genetic mutation. In the bone marrow, this process is known as clonal hematopoiesis, characterized by the overgrowth of blood cells with the same genetic mutation. Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant state where blood cells have acquired mutations but are not cancerous. There are several different genes that can be mutated in CHIP. CHIP is a risk factor for developing cancer, but the overall risk of actually progressing to cancer is low. CHIP is also associated with an increased risk of developing other diseases, including cardiovascular disease. While the presence of CHIP does not increase the risk of developing chronic lymphocytic leukemia (CLL), researchers wanted to know if it influences patient outcomes and progression to Richter transformation.
Methods and Participants:
DNA was extracted from the cells of patients with CLL at the time of their diagnosis. The samples were analyzed using next-generation sequencing.
Results:
- Samples were obtained and sequenced from 367 patients with CLL.
- CHIP mutations were more common in older patients.
- CHIP mutations were associated with shorter overall survival but not with shorter time to first treatment in patients with CLL.
- The overall presence of CHIP mutations was not associated with a higher risk of Richter transformation.
- However, the presence of one specific CHIP mutation (ASXL1) significantly increased the risk of developing Richter transformation.
- The presence of one type of CHIP mutation (SF3B1) was associated with an increased risk of atrial fibrillation (abnormal heart rhythm) in patients with CLL receiving BTK inhibitor therapy.
- The presence of non-DNMT3A CHIP mutations was associated with the development of more severe low neutrophil counts in patients with CLL being treated with venetoclax.
Conclusions:
While CHIP mutations have previously been shown not to affect the development of CLL, they may predispose patients to an increased risk of developing certain side effects in response to therapies such as BTK inhibitors and BCL2 inhibitors.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Prevalence and Clinical Impact of Clonal Hematopoiesis of Indeterminate Potential (CHIP) in Chronic Lymphocytic Leukemia and Richter Transformation.
