Loss of PALB2 predicts poor prognosis in acute myeloid leukemia and suggests novel therapeutic strategies targeting the DNA repair pathway

Antonella Padella, Maria Chiara Fontana, Giovanni Marconi, Eugenio Fonzi, Elisabetta Petracci, Anna Ferrari, Carmen Baldazzi, Cristina Papayannidis, Andrea Ghelli Luserna Di Rorá, Nicoletta Testoni, Gastone Castellani, Torsten Haferlach (+2 others)
2021 Blood Cancer Journal  
Dear Editor, Acute myeloid leukemia (AML) patients carrying complex karyotype or aneuploidies have a very poor prognosis, with a 5-year overall survival (OS) <20% 1 . We and others have shown that these patients are characterized by high genomic instability, along with defects of DNA damage response (DDR) genes 2,3 . Partner and localizer of BRCA2 (PALB2) is a key player in the homology recombination (HR) pathway, since it functions as a scaffold for the HR complex 4 . PALB2 monoallelic
more » ... monoallelic germline mutations are associated with an increased risk of developing breast, pancreatic, and ovarian cancers, whereas biallelic mutations lead to Fanconi anemia 5 . Genomic lesions, including sequence mutations and copy-number alterations (CNAs) of HR and DDR genes, are rare events in sporadic cancers and no recurrent genomic alterations in these genes have been reported so far in AML. Here, we studied the genomic alterations of PALB2 in AML, including its molecular interactions and prognostic relevance. Single-nucleotide polymorphism (SNP) arrays of 119 adult AML cases and whole-exome sequencing (WES) data of 68 adult AML cases were downloaded from the NGS-PTL project repository. Mutational data from the Beat-AML study (n = 531) and acute erythroid leukemia (AEL)
doi:10.1038/s41408-020-00396-x pmid:33414401 fatcat:s6c2mtutqrev3idqqabquu2aee