Aberrations on TP53, either as deletions of chromosome 17p (del17p) or mutations, are associated with poor outcome in multiple myeloma (MM), but conventional detection methods currently in use underestimate their incidence, hindering an optimal risk assessment and prognostication of MM patients. We have investigated the altered status of TP53 gene by SNPs array and sequencing techniques in a homogenous cohort of 143 newly diagnosed MM patients, evaluated both at diagnosis and at first relapse: single-hit on TP53 gene, either deletion or mutation, detected both at clonal and sub-clonal level, had a minor effect on outcomes. Conversely, the coexistence of both TP53 deletion and mutation, which defined the so-called double-hit patients, was associated with the worst clinical outcome (PFS: HR 3.34 [95% CI: 1.37–8.12] p = 0.008; OS: HR 3.47 [95% CI: 1.18–10.24] p = 0.02). Moreover, the analysis of longitudinal samples pointed out that TP53 allelic status might increase during the disease course. Notably, the acquisition of TP53 alterations at relapse dramatically worsened the clinical course of patients. Overall, our analyses showed these techniques to be highly sensitive to identify TP53 aberrations at sub-clonal level, emphasizing the poor prognosis associated with double-hit MM patients.

BRAFV600E mutation is the pathogenic driver of hairy cell leukemia (HCL) found in the vast majority of cases both at onset and during recurrences. The identification of the mutated allele in blood and marrow correlates with the presence of neoplastic cells and can be considered a marker of active disease. Likewise, the absence of the mutation after treatment may indicate a state of deep response. The BRAFV600E burden was measured by droplet digital polymerase chain reaction (ddPCR) and expressed as fractional abundance in 35 HCL patients at different stages of disease (onset, relapse, complete response [CR] after treatment, long‐term remission) in peripheral blood and/or bone marrow (when available). Mean values of fractional abundance for patients at diagnosis, relapse and response, respectively, were 12.26%, 16.52% and 0.02% in peripheral blood and 23.51%, 13.96% and 0.26% in bone marrow. Four patients out of 6 evaluated at response were molecularly negative for BRAFV600E in peripheral blood. Mean fractional abundance in peripheral blood tested in 14 patients with long lasting CR was 0.05%, and 10 patients were BRAFV600E negative. These preliminary results suggest that ddPCR permits to assess the active tumor burden in HCL at different disease phases and support the hypothesis that some patients in CR qualify for a molecular CR.

No abstract

Asthma is a complex and heterogeneous disease, caused by the interaction between genetic and environmental factors with a predominant allergic background in children. The role of specific genes in asthmatic bronchial reactivity is still not clear, probably because of the many common pathways shared with other allergic disorders. This study is focused on 11 SNPs possibly related to asthma that were previously identified in a GWAS study. The genetic variability of these SNPs has been analysed in a population of 773 Italian healthy controls, and the presence of an association between the polymorphisms and the asthma onset was evaluated performing genotyping analysis on 108 children affected with asthma compared with the controls. Moreover, a pool of 171 patients with only allergic rhinoconjunctivitis has been included in the case–control analysis. The comparison of allele frequencies in asthmatic patients versus healthy controls identified two SNPs—rs1162394 (p = 0.019) and rs25681 (p = 0.044)—associated with the asthmatic condition, which were not differentially distributed in the rhinoconjunctivitis group. The rs25681 SNP, together with three other SNPs, also resulted in not being homogenously distributed in the Italian population. The significantly higher frequency of the rs25681 and rs1162394 SNPs (located, respectively, in the C5 and SRGAP3 genes) in the asthmatic population suggests an involvement of these genes in the asthmatic context, playing a role in increasing the inflammatory condition that may influence asthma onset and clinical course.