TY - JOUR
T1 - Hematologic malignancies in Li–Fraumeni syndrome
T2 - A case report
AU - Bundrant, Bethany
AU - Gerstein, Yoheved
AU - Arun, Banu
AU - DiNardo, Courtney D.
N1 - Publisher Copyright:
© 2024 Wiley Periodicals LLC.
PY - 2024/7
Y1 - 2024/7
N2 - Li–Fraumeni syndrome (LFS) is a rare syndrome characterized by an increased lifetime risk of cancer development in multiple organ systems, typically caused by de novo or inherited germline pathogenic variants in the tumor suppressor TP53 gene. LFS is more classically associated with solid tumors; however, it is also associated with hematologic malignancies such as therapy-related acute myeloid leukemia (AML). We present the case of a female patient with a strong family and personal history of cancer who presented to our institution with therapy-related AML with next-generation sequencing showing a pathogenic TP53 mutation. She received several lines of systemic therapy and underwent stem cell transplant using her adult daughter as a haploidentical donor after achieving minimal residual disease (MRD). Her posttransplant bone marrow evaluations demonstrated persistence of the same pathogenic TP53 mutation despite ongoing clinical remission with full donor engraftment and negative MRD. Genetic testing was performed which confirmed the germline origin of the TP53 pathogenic variant in the patient. The patient's adult donor daughter was also identified to have the same pathogenic variant in TP53 consistent with LFS. The presented case highlights the need for increased awareness of LFS in the adult hematologic community, particularly for patients undergoing evaluation for stem cell transplant.
AB - Li–Fraumeni syndrome (LFS) is a rare syndrome characterized by an increased lifetime risk of cancer development in multiple organ systems, typically caused by de novo or inherited germline pathogenic variants in the tumor suppressor TP53 gene. LFS is more classically associated with solid tumors; however, it is also associated with hematologic malignancies such as therapy-related acute myeloid leukemia (AML). We present the case of a female patient with a strong family and personal history of cancer who presented to our institution with therapy-related AML with next-generation sequencing showing a pathogenic TP53 mutation. She received several lines of systemic therapy and underwent stem cell transplant using her adult daughter as a haploidentical donor after achieving minimal residual disease (MRD). Her posttransplant bone marrow evaluations demonstrated persistence of the same pathogenic TP53 mutation despite ongoing clinical remission with full donor engraftment and negative MRD. Genetic testing was performed which confirmed the germline origin of the TP53 pathogenic variant in the patient. The patient's adult donor daughter was also identified to have the same pathogenic variant in TP53 consistent with LFS. The presented case highlights the need for increased awareness of LFS in the adult hematologic community, particularly for patients undergoing evaluation for stem cell transplant.
KW - Li–Fraumeni syndrome
KW - stem cell transplant
KW - therapy-related acute myeloid leukemia
KW - TP53 mutation
UR - http://www.scopus.com/inward/record.url?scp=85186632267&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85186632267&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.63573
DO - 10.1002/ajmg.a.63573
M3 - Article
C2 - 38410872
AN - SCOPUS:85186632267
SN - 1552-4825
VL - 194
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 7
M1 - e63573
ER -