In chronic lymphocytic leukemia (CLL), TP53 gene aberrations due to chromosome 17p deletion ⌊del (17p)⌋ and/or TP53 gene mutation are associated with adverse prognosis and poor response to chemo (immuno) therapeutic regimens. Deletion and/or mutation of the TP53 gene occur on average in 10-15% of CLL patients before first-line treatment, and the incidence rises to 40-50% in refractory cases. TP53 mutations in the absence of del (17p) occur in a sizeable proportion of CLL patients (~5% in first-line treatment situations) and are also associated with significantly worse outcomes.
The survival of CLL patients with TP53 gene defects has improved dramatically with the introduction of B cell receptor (BcR) and BCL2 pathway inhibitors. Thus, chemoimmunotherapeutic regimens should be strictly avoided in patients positively tested for TP53 mutations or 17p deletions. TP53 gene disruptions maintain their negative prognostic impact with some targeted treatment regimens. The selection of appropriate treatment for patients with TP53 gene disruption is being debated and long-term follow-up is required before drawing definitive conclusions. The European Research Initiative on CLL (ERIC) recognizes that the correct assessment of both del (17p) and TP53 mutation before the first and subsequent lines of treatment is essential for patient management. ERIC has a longstanding interest in the standardization and harmonization of diagnostic techniques for such aberrations including FISH ⌊to detect del (17p)⌋ and molecular (to detect TP53 mutations) analyses, providing guidelines to the international scientific community (Pospisilova et al, Leukemia 2012; Malcikova et al, Leukemia, 2018).