Congenital dyserythropoietic anemia type II in a newborn with a novel compound heterozygous mutation in the SEC23B: a case report and review of the literature.

Congenital dyserythropoietic anemia type II (CDA II) refers to a group of extremely rare heterozygous disorders characterized by ineffective erythropoiesis and morphological abnormalities of erythrocytes and bone marrow erythroblasts. Six types of CDA with differing heterogenous genetic mutations have been identified to date. Due to the genetic and clinical heterogeneity of CDA, accurate diagnosis can be very challenging, especially with the clinical overlap observed between CDA and other dyserythropoietic diseases. A 1-month-old infant girl, born to a non-consanguineous family, presented with severe normocytic anemia that required transfusions every 2 to 3 weeks since birth, as well as jaundice. Whole exome sequencing revealed a novel compound heterozygosity in the SEC23B gene, thus establishing the diagnosis of CDA II. Analysis by multiple bioinformatics tools predicted that the mutant proteins were deleterious. Here, we report a novel variation in SEC23B that extends the mutation spectrum of SEC23B in the diagnosis of CDA II.

Intragenic ß-synuclein rearrangements in malignancy.

The synuclein family, consisting of α-, ß-, and γ-synuclein, is primarily expressed in neurons. Mutations of α- and ß-synuclein have been linked to Parkinson's disease and dementia with Lewy bodies, respectively. Recent studies have shown that synucleins are upregulated in various tumors, including breast, ovarian, meningioma, and melanoma, and high synuclein expression is associated with poor prognosis and drug resistance. We report a novel rearrangement of ß-synuclein in a pediatric T-cell acute lymphoblastic leukemia (T-ALL) case, where ß-synuclein (SNCB) is fused in-frame with ETS variant transcription factor 6 (ETV6), a gene frequently rearranged in acute leukemia including acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia (B-ALL), and T-ALL. An additional case of ß-synuclein rearrangement was identified in a squamous cell carcinoma of the lung through analysis of the public TCGA database. Both rearrangements involve the C-terminal of ß-synuclein. Since ß-synuclein shares extensive amino acid similarities with α-synuclein and α-synuclein binds to 14-3-3, an important regulator of apoptosis, the rearranged ß-synuclein may contribute to tumorigenesis by deregulating apoptosis. In addition, overexpression of synucleins has been shown to increase cell proliferation, suggesting that the rearranged ß-synuclein may also deregulate the cell cycle.

Prognostic significance of steroid response in pediatric acute lymphoblastic leukemia: The CCCG-ALL-2015 study.

Introduction: Whether steroid response is an independent risk factor for acute lymphoblastic leukemia (ALL) is controversial. This study aimed to investigate the relationship between response to dexamethasone and prognosis in children with ALL. Methods: We analyzed the data of 5,161 children with ALL who received treatment in accordance with the Chinese Children's Cancer Group ALL-2015 protocol between January 1, 2015, and December 31, 2018, in China. All patients received dexamethasone for 4 days as upfront window therapy. Based on the peripheral lymphoblast count on day 5, these patients were classified into the dexamethasone good response (DGR) and dexamethasone poor response (DPR) groups. A peripheral lymphoblast count ≥1× 109/L indicated poor response to dexamethasone. Results: The age, white blood cell counts, prevalence of the BCR/ABL1 and TCF3/PBX1 fusion genes, and rates of recurrence in the central nervous system were higher in the DPR than in the DGR group (P<0.001). Compared to the DPR group, the DGR group had a lower recurrence rate (18.6% vs. 11%) and higher 6-year event-free survival (73% vs. 83%) and overall survival (86% vs. 92%) rates; nevertheless, subgroup analysis only showed significant difference in the intermediate-risk group (P<0.001). Discussion: Response to dexamethasone was associated with an early treatment response in our study. In the intermediate-risk group, dexamethasone response added a prognostic value in addition to minimal residual disease, which may direct early intervention to reduce the relapse rate.