Background: Acute lymphoblastic leukemia (ALL), the most common childhood malignancy, is characterized by recurring structural chromosomal alterations and genetic alterations, whose detection is critical in diagnosis, risk stratification and prognostication. However, the genetic mechanisms that give rise to ALL remain poorly understood. Methods: Using next-generation sequencing (NGS) in matched germline and tumor samples from 140 pediatric Chinese patients with ALL, we landscaped the gene mutations and estimated the mutation frequencies in this disease. Results: Our results showed that the top driver oncogenes having a mutation prevalence over 5% in childhood ALL included KRAS (8.76%), NRAS (6.4%), FLT3 (5.7%) and KMT2D (5.0%). While the most frequently mutated genes were KRAS, NRAS and FLT3 in B cell ALL (B-ALL), the most common mutations were enriched in NOTCH1 (23.1%), FBXW7 (23.1%) and PHF6 (11.5%) in T cell ALL (T-ALL). These mutant genes are involved in key molecular processes, including the Ras pathway, the Notch pathway, epigenetic modification, and cell-cycle regulation. Strikingly, more than 50% of mutations occurred in the high-hyperdiploid (HeH) ALL existed in Ras pathway, especially FLT3 (20%). We also found that the epigenetic regulator gene KMT2D, which is frequently mutated in ALL, may be involved in driving leukemia transformation, as evidenced by an in vitro functional assay. Conclusion: Overall, this study provides further insights into the genetic basis of ALL and shows that Ras mutations are predominant in childhood ALL, especially in the high-hyperdiploid subtype in our research.

The relation between agranular reticulum and glycogen was studied in hepatic cells of female rats. Prolonged fasting of nonadrenalectomized rats did hot result ins complete liver glycogen depletion, whereas in adrenalectomized rats this could be accomplished within a few hours of fasting. In nonadrenalectomized rats a marked development of agranular reticulum associated with glycogen was found, whereas in adrenalectomized rats no such marked development of agranular reticulum was seen during glycogen depletion. Early glycogen restoration in glycogen-depleted liver cells of adrenalectomized rats was brought about 2-4 hr after the injection of 1 dose of cortisone or ½-1 hr after the injection of glucose. Early restoration of glycogen was accompanied and even preceded by a marked development of tubular agranular reticulum. A probable role of this organelle in glycogen synthesis and breakdown is discussed. High resolution autoradiography of tritium-labeled glucose incorporation offered some further illustration on the process of glycogen formation.

Summary. A case of hairy‐cell leukaemia was studied by conventional cyto‐chemical, electronmicroscopic and immunofluorescence techniques. This condition is often known as leukaemic reticuloendotheliosis (LRE) but the nature of the proliferating cells has been in doubt. The accumulation of immunoglobulin‐synthesizing cells in the peripheral blood suggests that the involved cells are lymphocytes and no evidence for a reticular or endothelial origin of the LRE cell could be found.

BackgroundSubcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a malignant primary T-cell lymphoma that is challenging to distinguish from autoimmune disorders and reactive panniculitides. Delay in diagnosis and a high misdiagnosis rate affect the prognosis and survival of patients. The difficulty of diagnosis is mainly due to an incomplete understanding of disease pathogenesis.MethodsWe performed single-cell RNA sequencing of matched subcutaneous lesion tissue, peripheral blood, and bone marrow from a patient with SPTCL, as well as peripheral blood, bone marrow, lymph node, and lung tissue samples from healthy donors as normal controls. We conducted cell clustering, gene expression program identification, gene differential expression analysis, and cell-cell interaction analysis to investigate the ecosystem of SPTCL.ResultsBased on gene expression profiles in a single-cell resolution, we identified and characterized the malignant cells and immune subsets from a patient with SPTCL. Our analysis showed that SPTCL malignant cells expressed a distinct gene signature, including chemokines families, cytotoxic proteins, T cell immune checkpoint molecules, and the immunoglobulin family. By comparing with normal T cells, we identified potential novel markers for SPTCL (e.g., CYTOR, CXCL13, VCAM1, and TIMD4) specifically differentially expressed in the malignant cells. We also found that macrophages and fibroblasts dominated the cell-cell communication landscape with the SPTCL malignant cells.ConclusionsThis work offers insight into the heterogeneity of subcutaneous panniculitis-like T-cell lymphoma, providing a better understanding of the transcription characteristics and immune microenvironment of this rare tumor.

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