TP53 mutations are early events in chronic lymphocytic leukemia disease progression and precede evolution to complex karyotypes

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TP53 abnormalities lead to resistance to purine analogues and are found in over 40% of patients with refractory chronic lymphocytic leukemia (CLL). At diagnosis, no more than 5% of patients carry the 17p deletion, most cases harbour mutations within the other TP53 allele. The incidence of a TP53 mutation as the only alteration is approximately 5%, but this depends on the sensitivity of the technique. Recently, having a complex karyotype has been considered a strong adverse prognostic factor. However, there are no longitudinal studies simultaneously examining the presence of the 17p deletion, TP53 mutations and karyotype abnormalities. We conducted a retrospective longitudinal study of 31 relapsed/refractory CLL patients. Two to six blood samples per patient were analyzed, with a median follow-up of 8 years. In this report, we assessed the sequence of events of TP53 clonal evolution and correlated the presence of TP53 abnormalities to genetic instability during progression and treatment. Next-generation sequencing allowed the early detection of TP53 mutated clones and was able to be performed on a routine basis, demonstrating an excellent correlation between the Illumina and Ion Torrent technologies. We concluded that TP53 mutations are early events and precede clonal evolution to complex karyotypes. We strongly recommend the early and iterated detection of TP53 mutations in progressive cases.

What's New?

For patients with chronic lymphocytic leukemia, possessing multiple chromosomal abnormalities means bad news. Could there be a way to predict genomic instability before it happens? These authors investigated whether mutations in TP53 might presage the onset of chromosomal abnormalities. They conducted a longitudinal study, in which they followed 31 CLL patients over a period of several years. It turned out that mutations in TP53 occur early and precede the genomic instability that generates chromosomal abnormalities and hinders recovery. Thus, searching for TP53 mutations could identify those patients likely to develop additional chromosomal defects and poor outcomes.

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