ABSTRACT
TP53 aberrations predict chemoresistance and represent a contraindication for the use of standard chemoimmunotherapy in chronic lymphocytic leukaemia (CLL). Recent next-generation sequencing (NGS)-based studies have identified frequent low-burden TP53 mutations with variant allele frequencies below 10%, but the clinical impact of these low-burden TP53 mutations is still a matter of debate. In this study, we aimed to scrutinise the subclonal architecture and clinical impact of TP53 mutations using a sensitive, NGS-based mutation analysis in a 'real-world' cohort of 901 patients with CLL. In total, 225 TP53 mutations were identified in 17.5% (158/901) of the patients; 48% of these alterations represented high-burden mutations, while 52% were low-burden TP53 mutations. Low-burden mutations as sole alterations were identified in 39% (62/158) of all mutated cases with 82% (51/62) of these being represented by a single low-burden TP53 mutation. Patients harbouring low-burden TP53 mutations had significantly lower time to first treatment compared to patients with wild-type TP53. Our study has expanded the knowledge on the frequency, clonal architecture, and clinical impact of low-burden TP53 mutations. By demonstrating that patients with sole low-burden TP53 variants represent more than one-third of patients with TP53 mutations and have an increased risk for treatment initiation, our findings strengthen the need to redefine the threshold of TP53 variant reporting to below 10% in the routine diagnostic setting.
Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Mutation , Immunotherapy , Tumor Suppressor Protein p53/geneticsABSTRACT
The agranular CD4+/CD56+ haematodermic neoplasm (so-called blastic NK-cell lymphoma) represents a distinct clinicopathologic entity and it is characterised by its clinical presentation (skin tropism, bone marrow involvement with or without leukemic phase, very poor prognosis) and the common expression of the T helper CD4 as well as the NK cell marker CD56. The authors present an 86 year old male patient with hemorrhagic macules, plaques and hemorrhagic flat nodules mainly on the trunk without any complaints. The skin biopsy revealed an agranular CD4+/CD56+ hematodermic tumor. During the medical check-up and the 18 months long follow-up they did not find any internal involvement including the bone marrow. In their case they revealed the cutaneous form of the hematodermic tumor which is considered to be a new and interesting manifestation of aleukemic leukemia cutis.
