期刊
SCIENTIFIC REPORTS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41598-022-14364-x
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资金
- Academy of Finland [322675, 137680, 274474]
- Sigrid Juselius Foundation
- Finnish Special Governmental Subsidy for Health Sciences, Research, and Training
- Helsinki University Hospital Comprehensive Cancer Research Funding
- Finnish Funding Agency for Technology and Innovation (TEKES)
- Vare Foundation for Pediatric Cancer Research
- Swedish Childhood Cancer Foundation
- Cancer Foundation Finland
- Foundation for Pediatric Research (Finland)
- Ane and Signe Gyllenberg Foundation
- Orion Research Foundation
- Ida Montin Foundation
- Finnish Hematology Association
- Biomedicum Helsinki Foundation
- Paulo Foundation
- Paivikki and Sakari Sohlberg Foundation
- iCAN Digital Precision Cancer Medicine
- Academy of Finland (AKA) [322675, 274474, 137680, 137680, 322675, 274474] Funding Source: Academy of Finland (AKA)
Despite progress in ALL therapies, a significant subset of patients have poor prognosis. Research revealed that germline variants associated with predisposition to ALL are prevalent in patients, especially in adults. Acknowledging genetic factors is crucial for patient care and post-therapy follow-up.
Despite recent progress in acute lymphoblastic leukemia (ALL) therapies, a significant subset of adult and pediatric ALL patients has a dismal prognosis. Better understanding of leukemogenesis and recognition of germline genetic changes may provide new tools for treating patients. Given that hematopoietic stem cell transplantation, often from a family member, is a major form of treatment in ALL, acknowledging the possibility of hereditary predisposition is of special importance. Reports of comprehensive germline analyses performed in adult ALL patients are scarce. Aiming at fulfilling this gap of knowledge, we investigated variants in 93 genes predisposing to hematologic malignancies and 70 other cancer-predisposing genes from exome data obtained from 61 adult and 87 pediatric ALL patients. Our results show that pathogenic (P) or likely pathogenic (LP) germline variants in genes associated with predisposition to ALL or other cancers are prevalent in ALL patients: 8% of adults and 11% of children. Comparison of P/LP germline variants in patients to population-matched controls (gnomAD Finns) revealed a 2.6-fold enrichment in ALL cases (CI 95% 1.5-4.2, p = 0.00071). Acknowledging inherited factors is crucial, especially when considering hematopoietic stem cell transplantation and planning post-therapy follow-up. Harmful germline variants may also predispose patients to excessive toxicity potentially compromising the outcome. We propose integrating germline genetics into precise ALL patient care and providing families genetic counseling.
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