Clinical and molecular profiling of AML patients with chromosome 7 or 7q deletions in the context of TP53 alterations and venetoclax treatment

Abstract

Deletions in chromosome 7 (del(7)) or its long arm (del(7q)) constitute the most common adverse cytogenetic events in acute myeloid leukemia (AML). We retrospectively analyzed 243 treatment-naive patients with AML and del(7) (168/243; 69%) or del(7q) (75/243; 31%) who did not receive any myeloid-directed therapy prior to AML diagnosis. This is the largest comprehensive clinical and molecular analysis of AML patients with del(7) and del(7q). Our results show that relapse-free survival was significantly longer for AML patients with del(7q) compared to del(7), but the overall survival and remission duration were similar. TP53 mutations and del5/5q were the most frequent co-occurring mutations and cytogenetic abnormalities, and conferred worse outcomes in del(7) and del(7q) patients. Venetoclax-based treatments were associated with worse outcomes in TP53 mutated AML patients with del(7) or del(7q), as well as del(7) with TP53 wildtype status, requiring further investigation.

Keywords:

• Myeloid leukemias and dysplasias
• TP53
• AML
• chr7 del
• chr7q del
• venetoclax

Disclosure statement

Naval Daver: research grants and consultancy fees from Daiichi-Sankyo Bristol-Meyers Squibb, Pfizer, Gilead, Servier, Genentech, Astellas, AbbVie, ImmunoGen, Amgen, Trillium, Hanmi, Trovagene, FATE Therapeutics, Novimmune, Glycomimetics, Arog, Novartis, Jazz, Celgene, Syndax, Shattuck Labs, and Agios. Elias Jabour: research grants and consultancy fees from Amgen, Adaptive biotechnologies, Pfizer, BMS, Takeda, Abbvie, Novartis, BMS, and Genentech. Hussein Abbas: consultancy fees from Molecular Partners.

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon request.

Additional information

Funding

This work was partially funded by partial funding to HAA from Ladies Leukemia League Foundation, Conquer Cancer Foundation Young Investigator Award and MD Anderson Institutional Start-up Grant. EA was supported by the CPRIT Training Award (RP210028), and NIH NCI (F32CA271697).