Researchers investigated the effects of genetic alterations in adult T-cell leukemia and lymphoma (ATL) on disease phenotypes and clinical outcomes, published in Blood (January 2018;131:215-225).
ATL is a group of peripheral T-cell malignancies whose genetic profile has been investigated extensively. However, it is relatively unknown how genetic alterations in ATL can affect clinical features and prognosis.
A group of Japanese researchers led by Keisuke Kataoka, department of pathology and tumor biology, graduate school of medicine, Kyoto University, conducted a study to better understand how genetic alterations commonly found in ATL may affect disease phenotypes and clinical outcomes. Researchers sampled genotyping data from 414 and 463 patients with ATL using targeted-capture sequencing and single nucleotide polymorphism array karyotyping, respectively.
Researchers noted that aggressive disease subtypes were associated with an increased burden of genetic and epigenetic alterations, higher frequencies of TP53 and IRF4 mutations, and a variety of copy number alterations (eg, PD-L1 amplifications and CDKN2A deletions), compared with indolent disease subtypes. Only STAT3 mutation was found to be associated with indolent ATL.
Higher number of somatic mutations and copy number alterations were reportedly associated with worse survival. A multivariate analysis incorporating both clinical factors and genetic alterations revealed that the Japan Clinical Oncology Group prognostic index high-risk, older age, PRKCB mutations, and PD-L1 amplifications were independent prognostic factors of poor survival in aggressive ATL. Furthermore, IRF4 mutations, PD-L1 amplifications, and CDKN2A deletions were significantly associated with shorter survival in indolent ATL, though chronic disease subtype with unfavorable clinical factors was only marginally significant.
The study’s findings led researchers to conclude that somatic alterations characterizing aggressive disease indicate worse prognosis in indolent ATL. PD-L1 amplifications are a strong genetic predictor for worse outcome in both aggressive and indolent ATL, they added.
“ATL subtypes are further classified into molecularly distinct subsets with different prognosis,” researchers wrote. “Genetic profiling might contribute to improved prognostication and management of [patients with ATL].”—Zachary Bessette