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Therapy-Related Myeloid Neoplasms: Predisposition and Clonal Evolution.
Emiliano Fabiani1,2, A Cristiano1, H Hajrullaj1
1Department of Biomedicine and Prevention, University of Tor Vergata, Rome, Italy.
Mediterranean Journal of Hematology and Infectious Diseases
|November 29, 2023
Summary
Therapy-related Myeloid Neoplasms (t-MN) are a serious consequence of cancer treatment, particularly in aging populations. Understanding risk factors like genetic predispositions and Clonal Hematopoiesis of Indeterminate Potential (CHIP) is crucial for managing this emerging health problem.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Therapy-related Myeloid Neoplasms (t-MN) are severe long-term complications of cytotoxic therapies for primary cancers and autoimmune diseases.
- t-MN presents a significant clinical challenge due to poor survival rates and resistance to current treatments, increasingly affecting aging populations with improved life expectancies.
- The complexity of t-MN pathogenesis is influenced by diverse primary tumors, varied therapeutic strategies, and novel drug development.
Purpose of the Study:
- To elucidate the multifaceted risk factors contributing to the development of therapy-related Myeloid Neoplasms.
- To explore the role of genetic predispositions and Clonal Hematopoiesis of Indeterminate Potential (CHIP) in t-MN pathogenesis.
- To understand the dynamic process of clonal evolution in the progression from preleukemic states to t-MN.
Main Methods:
- Review and synthesis of current research on t-MN risk factors.
- Analysis of data from deep sequencing techniques to identify germline variants in t-MN patients.
- Investigation of the association between Clonal Hematopoiesis of Indeterminate Potential (CHIP) and t-MN development.
Main Results:
- Risk factors for t-MN can be categorized into patient-specific, inherited, and acquired predispositions, with risk increasing with age and comorbidities.
- Germline variants are identified in 15-20% of t-MN patients, underscoring their role in cancer predisposition.
- t-MN with driver mutations may emerge from a background of CHIP, influenced by selective pressures from chemotherapy and radiation, with clonal evolution playing a key role.
Conclusions:
- Therapy-related Myeloid Neoplasms represent a growing clinical concern, particularly in aging demographics.
- Genetic factors, including germline variants and CHIP, significantly contribute to t-MN susceptibility and development.
- Understanding clonal evolution is vital for comprehending the progression from preleukemic conditions to overt t-MN.
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