Photo Credit: Md Babul Hosen

The following is a summary of “Genomic characterization of AML with aberrations of chromosome 7: a multinational cohort of 519 patients,” published in the August 2024 issue of Hematology by Halik et al.

Researchers conducted a retrospective study to characterize the genomic landscape and prognostic implications of chromosome 7 (chr7) deletions and partial losses in the context of other genetic aberrations in acute myeloid leukemia (AML).

Using whole-exome sequencing in the exploration cohort, they investigated 60 paired diagnostic/remission samples of adult patients with AML and chromosome 7 aberrations [abn(7)]. A gene panel with 66 genes and an SNP backbone was designed and used on the remaining validation samples. Of 519 patients, 415 received intensive induction treatment, usually with cytarabine and anthracyclines.

The results showed that TP53 was the most frequently mutated gene in the exploration cohort at 33%, followed by epigenetic regulators (DNMT3A, KMT2C IDH2) and signaling genes (NRAS, PTPN11). Of 519 patients, 30% had ≥1 mutation in genes commonly deleted on chromosome 7, most often KMT2C (16%) and EZH2 (10%). The KMT2C mutations were typically subclonal and more common in patients with del(7q) or de novo/core-binding factor AML (45%), TP53 mutations were primarily disease-initiating events, while del(7q) or −7 were subclonal in one-third of cases. Multivariable analysis found 5 key genetic lesions with significant prognostic impact in patients with AML and ABN (7), TP53 and PTPN11 mutations (11%) were linked to poor OS (OS; TP53: HR, 2.53; P<0.001; PTPN11: HR, 2.24; P<0.001) and relapse-free survival (RFS; TP53: HR, 2.3; P=0.008; PTPN11: HR, 2.32; P=0.003), IDH2 mutations (9%) were associated with longer OS (HR, 0.51; P=0.0015) and better RFS (HR, 0.5; P=0.036).

Investigators identified novel genetic lesions and provided a comprehensive overview of recurrent gene mutations and the clinical relevance in AML with chromosome 7 abnormalities, highlighting KMT2C as a potential therapeutic target.

Source: jhoonline.biomedcentral.com/articles/10.1186/s13045-024-01590-1