Case report: TP53 c.848G>A germline mutation as a possible screening target at initial diagnosis for acute lymphoblastic leukemia.

BACKGROUD: Li-Fraumeni syndrome is a hereditary tumor syndrome characterized by an elevated risk of malignancy, particularly acute lymphoblastic leukemia (ALL), which can be caused by the heterozygous germline mutation. TP53 gene germline mutation is considered a potential risk factor and crucial prognostic parameter for acute leukemia development and diagnosis, but rarely occurs in adults, and its specific pathogenic significance in acute leukemia is unclear. CASE PRESENTATION: We describes a case of a 45-year-old woman diagnosed with ALL. Whole-exome sequencing approach identified one of the TP53 germline mutations from her bone marrow sample with possible pathogenic significance, c.848G>A (p.Arg283His) heterozygous missense mutation located on exon 8, which was further verified in her hair, oral mucous and nail samples. Family pedigree screening revealed that the same TP53 genetic variant was present in the patient's father and non-donor son, whereas not in the donor. Digital PCR observed that this point mutation frequency dropped post-transplantation but remained low during maintenance therapy when the patient was leukemia-free. CONCLUSION: This suspected Li-Fraumeni syndrome case report with a likely pathogenic heterozygous TP53 variant expands the cancer genetic spectrum. Screening her family members for mutations facilitates identifying the optimal relative donor and avoids unnecessary treatment by monitoring TP53 germline mutations for minimal residual disease following hematopoietic stem cell transplantation. Its potential roles in hematological malignant tumor development and clinical pathogenic implications necessitate further probing.

[Introplasmic IFN-γ level in circulating T cells detected by flow cytomertry and its relation with treatment efficiency in the patients with aplastic anemia].

This study was aimed to investigate the effects of the introplasmic interferon-γ level in circulating T cell of patients with aplastic anemia (AA) and its clinical significance. The interferon-γ level before and after immuno-suppressive therapy was monitored by flow cytometry. The results indicated that the higher interferon-γ level was detected in 28 out of 50 AA patients, detected rate was 56%. The effective rate of immunosuppressive therapy for AA patients with higher interferon-γ level was up to 85.7% (24/28). The decrease of interferon-γ level in these patients positively correlated with hemogram recovery to normal level and obviously earlier than hematologic remission. It is concluded that the immunosuppressive therapy shows better efficacy for AA patients with high interferon-γ level, moreover the change of interferon-γ level is earlier than hematologic change, that is important for predicting the therapeutic efficacy and relapse of disease.