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HLA‐B*55:130 differs from HLA‐B*55:35 by two nucleotides in exon 2. [ABSTRACT FROM AUTHOR]

HLA‐DQB1*06:208:02 differs from HLA‐DQB1*06:02:02 by one nucleotide in exon 2. [ABSTRACT FROM AUTHOR]

HLA‐DRB1*13:306 differs from HLA‐DRB1*13:02:01:01 in exon 2 in codon 84 by a single coding change. [ABSTRACT FROM AUTHOR]

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.

Objective: To establish a new digital polymerase chain reaction (dPCR) system for the detection of BCR-ABL fusion gene in patients with chronic myeloid leukemia (CML), and explore its analytical performance and clinical applicability in the detection of BCR-ABL p190/210/230 ., Methods: A new dPCR system for detecting BCR-ABL p190/210/230 was successfully developed, and its sensitivity difference with qPCR and improvement of drug side effects in patients with CML during drug reduction or withdrawal were compared., Results: Among 176 samples, qPCR and dPCR showed high consistency in the sensitivity of detecting BCR-ABL (82.39%), and the positive rate of dPCR was about 5 times higher that of qPCR (20.45% vs 3.98%). During follow-up, blood routine (25% vs 10%), kidney/liver/stomach (25% vs 20%) and cardiac function (10% vs 0) were significantly improved after drug reduction or withdrawal in patients with initial dPCR negative compared with before drug reduction or withdrawal., Conclusions: This new dPCR detection system can be applied to the detection of BCR-ABL p190/210/230 . It has better consistency and higher positive detection rate than qPCR. Drug withdrawal or dose reduction guided by dPCR has a certain effect on improving drug side effects.

HLA-DRB1*12:01:12 differs from HLA-DRB1*12:01:01:01 by one nucleotide in exon 2., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Antiepileptic drugs frequently cause cutaneous adverse reactions (cADRs). Numerous studies have reported associations between human leukocyte antigen (HLA) alleles and cADRs caused by single antiepileptic drug in Southern Han Chinese people. However, the relationship between the HLA allele and cADRs sequentially induced by two or more antiepileptic drugs (AEDs-induced cross-reactivity) is unclear. To explore the associations between HLA alleles and AEDs-induced cross-reactivity, we prospectively recruited patients with AEDs-induced cross-reactivity from 2009 to 2017 and performed high-resolution genotyping to detect the HLA-A, B, C, and DRB1 alleles in patients for comparison with normal controls. To verify the important genotype, we compared its presence in patients with cross-reactivity to enlarged normal controls, and its presence in patients with carbamazepine (CBZ)-induced maculopapular exanthema (MPE) to CBZ-tolerant controls. Further, the important allele was replicated by meta-analysis. Twenty-three patients with AED-induced cross-reactivity and 500 healthy individuals were enrolled from Southern China. All patients had a mild rash without mucosal or systemic involvement. The HLA-B * 13:01 allele was present in 34.78% (8/23) of patients, 14.60% (73/500) of healthy individuals, and 14.5% (763/5,270) healthy individuals, revealing a significant association (8/23 vs. 73/500; P = 0.02; OR: 3.12; 95% CI: 1.28-7.62; 8/23 vs. 763/5,270; P = 0.014; OR: 3.15; 95% CI: 1.33-7.46). HLA-B * 13:01 was presented numerically higher in CBZ-induced MPE than that in CBZ-tolerant individuals without statistical significance (33/145, 22.76%, vs. 28/179, 15.64%; P = 0.103). Meta-analysis revealed an association between HLA-B * 13:01 and cADRs induced by single AEDs or/and non-AEDs in Chinese and Thai populations ( P = 0.000). This study suggests that HLA-B * 13:01 is potentially associated with AED-cADRs in general, possibly with stronger effect in cross-reactivity. Screening for HLA-B * 13:01 prior to starting AEDs therapy may help to avoid cADRs. However, this association requires further analysis in a multi-center study with a larger sample size.