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Introduction: Relapse remained the major obstacle to improving the prognosis of children with acute lymphoblastic leukemia (ALL). This study aimed to investigate the changing patterns of Ig/TCR gene rearrangements between diagnosis and relapse and the clinical relevance and to explore the mechanism of leukemic relapse. Methods: Clonal Ig/TCR gene rearrangements were screened by multiplex PCR amplification in 85 paired diagnostic and relapse bone marrow (BM) samples from children with ALL. The new rearrangements presented at relapse were quantitatively assessed by the RQ‐PCR approach targeting the patient‐specific junctional region sequence in 19 diagnostic samples. The relapse clones were further back‐traced to diagnostic and follow‐up BM samples from 12 patients. Results: Comparison of Ig/TCR gene rearrangements between diagnosis and relapse showed that 40 (57.1%) B‐ALL and 5 (33.3%) T‐ALL patients exhibited a change from diagnosis to relapse, and 25 (35.7%) B‐ALL patients acquired new rearrangements at relapse. The new relapse rearrangements were present in 15 of the 19 (78.9%) diagnostic samples as shown by RQ‐PCR, with a median level of 5.26 × 10−2. The levels of minor rearrangements correlated with B immunophenotype, WBC counts, age at diagnosis, and recurrence time. Furthermore, back‐tracing rearrangements in 12 patients identified three patterns of relapse clone dynamics, which suggested the recurrence mechanisms not only through clonal selection of pre‐existing subclones but also through an ongoing clonal evolution during remission and relapse. Conclusion: Backtracking Ig/TCR gene rearrangements in relapse clones of pediatric ALL revealed complex patterns of clonal selection and evolution for leukemic relapse. [ABSTRACT FROM AUTHOR]

Peter H. L. Chang came to power in Northeast China and served concurrently as the president of Northeastern University in 1928. He believed that the prosperity of the country lay in cultivating new talent, and he donated his private property to develop tertiary education many times, which reflected his thoughts in tertiary education such as attracting people of talent, giving preferential treatment to them, and putting talented persons in important positions. Finally he made Northeastern University become one of the domestic first-class universities in the early thirties. We can make a deeper understanding of Peter H. L. Chang's patriotic spirit which was helpful for today's tertiary education by analyzing the outlook on talent of Peter H. L. Chang. [ABSTRACT FROM AUTHOR]

Chinese central government organized by KMT was beginning to penetrate and control the Northeastern University since Peter H. L. Chang declared that the Northeast China begun coming within the jurisdiction of China's central government in 1928, though the region was only a norminal part of China. The university then moved into Peiping and was hard up after the "September Eighteenth Incident". The central government seized the opportunity to support financially the university so as to control it further, but it was norminally a "National University" at that time. After the "Xi'an Incident", KMT regulated the university all-inclusively and took it over in the end. Thus, the Northeastern University became fully a national university. Such a nationalization process of the university was full of the contradictory interaction between KMT and the local forces and the rival fractions within the university --both affected the university's development profoundly. [ABSTRACT FROM AUTHOR]

Context.—: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm that predominantly affects young children., Objective.—: To investigate genetic alterations and their correlation with clinical characteristics and prognosis in pediatric LCH., Design.—: We performed targeted sequencing to detect mutations in LCH lesions from pediatric patients., Results.—: A total of 30 genomic alterations in 5 genes of the MAPK pathway were identified in 187 of 223 patients (83.9%). BRAF V600E (B-Raf proto-oncogene, serine/threonine kinase) was the most common mutation (51.6%), followed by MAP2K1 (mitogen-activated protein kinase kinase 1) alterations (17.0%) and other BRAF mutations (13.0%). ARAF (A-Raf proto-oncogene, serine/threonine kinase) and KRAS (KRAS proto-oncogene, GTPase) mutations were relatively rare (2.2% and 0.9%, respectively). Additionally, FNBP1 (formin-binding protein 1)::BRAF fusion and MAP3K10 (mitogen-activated protein kinase kinase 10) mutations A17T and R823C were identified in 1 case each, with possible constitutive activation of ERK1/2 phosphorylation. BRAF V600E was more frequent in patients with risk organ involvement, while MAP2K1 mutation was more prevalent in patients with single-system LCH (P = .001). BRAF V600E was associated with craniofacial bone, skin, liver, spleen, and ear involvement (all P < .05). Patients with other BRAF mutations had a higher proportion of spinal column involvement (P = .006). Univariate analysis showed a significant difference in progression-free survival among the 4 molecular subgroups for patients treated with first-line therapy (P = .02). According to multivariate analysis, risk organ involvement was the strongest independent adverse prognostic factor (hazard ratio, 8.854; P < .001); BRAF or MAP2K1 mutation was not an independent prognostic factor., Conclusions.—: Most pediatric patients with LCH carry somatic mutations involving the MAPK pathway, correlating with clinical characteristics and outcomes for first-line chemotherapy., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)