OBJECTIVE: To explore the clinical manifestations, diagnosis, treatment and prognosis of blastic plasmacytoid dendritic cell neoplasm(BPDCN). METHODS: The clinical features, bone marrow morphology and immunophenotyping, treatment and prognosis of 4 patients with BPDCN were analyzed retrospectively. RESULTS: 4 patients had bone marrow， spleen and lymph nodes involvement， 2 patients had skin lesions， and 3 patients had central nervous system infiltration． Tailing phenomenon of abnormally cells could be seen in bone marrow. The immunophenotyping showed that CD56, CD4 and CD123 expression was observed in 4 patients， and CD304 in 3 patients． One patient refused chemotherapy and died early. Both patients achieved complete remission after the initial treatment with DA+VP regimen, 1 of them achieved complete remission after recurrence by using the same regimen again． One patient failed to respond to reduced dose of DA+VP chemotherapy, and then achieved complete remission with venetoclax+azacitidine. CONCLUSION The malignant cells in BPDCN patients often infiltrate bone marrow, spleen and lymph nodes, and have specical phenotypes, with poor prognosis. The treatment should take into account both myeloid and lymphatic systems. The treatment containing new drugs such as BCL-2 inhibitors combined with demethylation drugs is worth trying.
Humans ; Dendritic Cells ; Retrospective Studies ; Skin Neoplasms/pathology* ; Antineoplastic Agents/therapeutic use* ; Bone Marrow/pathology* ; Myeloproliferative Disorders ; Hematologic Neoplasms/drug therapy*

OBJECTIVE: To investigate the clinicopathological features of blastic plasmacytoid dendritic cell neoplasm (BPDCN). METHODS: A total of 13 cases of BPDCN diagnosed in Peking University First Hospital from January 2013 to March 2022 were collected. The clinical features, histopathological characteristics, immunophenotypes and prognosis of the patients were analyzed retrospectively, and the related literatures was reviewed as well. RESULTS: Among the 13 patients, 11 were male and 2 were female, with a median age of 62 years (ranging from 5 to 78 years). Among them, single organ involvement occurred in 5 cases, all of which presented with skin lesions. Two or more organs were involved in other 8 cases (single organ with bone marrow involved in 3 cases; skin, bone marrow and lymph node involved simultaneously in 3 cases; skin, bone marrow, lymph node and spleen involved simultaneously in 2 cases). Histopathologically, it was characterized by the proliferation of medium to large atypical blastic cells, which infiltrated the whole thickness of dermis. When involved, the bone marrow lesions mainly appeared in a diffuse pattern, while the lymph node structure was usually destroyed, and the red pulp of the affected spleen was diffusely invaded. Immunohistochemical staining showed that all the 13 cases were positive for CD4, CD56, and CD123 (13/13) in varying degrees. All the 9 cases expressed TCL1 (9/9). Variable expression of CD68 (KP1) (8/13), TdT (7/12), CD117 (2/6), and high Ki-67 proliferation index (40%~80%) were showed. The neoplastic cells lacked expressions of CD20, CD3, MPO, CD34, or CD30; EBER in situ hybridization were negative (0/9). After definite diagnosis, 6 cases received chemotherapy, among which 1 received adjuvant radiotherapy, and 2 received subsequent bone marrow transplantation. Another 2 cases only received maintenance treatment. The median follow-up time was 14 months (ranging from 6 to 36 months), 5 patients died of the disease (6 to 18 months), 3 patients survived (7 to 36 months up to now), and the remaining 5 patients lost follow-up. CONCLUSION BPDCN is a rare type of malignant lymphohematopoietic tumor with aggressive behavior and poor prognosis. The diagnosis should be made combining clinical features, histopathology, and immunohistochemical phenotype. Attention should be paid to differentiating BPDCN from other neoplasms with blastoid morphology or CD4+CD56+ tumors.
Male ; Female ; Humans ; Hematologic Neoplasms ; Retrospective Studies ; Dendritic Cells ; Skin Neoplasms/pathology* ; Skin/pathology*

OBJECTIVE: To explore the clinical characteristics, treatment, and prognosis of patients with blastic plasmacytoid dendritic cell neoplasm(BPDCN). METHODS: Clinical data of 5 patients diagnosed with BPDCN in Wuhan First Hospital and Wuhan Tongji Hospital from June 2016 to November 2021 were retrospectively analyzed. RESULTS: Among the 5 patients, 3 were male and 2 were female, with a median age of 28(10-52) years old. Four patients showed obvious skin damage at the initial diagnosis; the other one showed clinical manifestations of acute leukemia rather than obvious skin damage at the initial diagnosis, but infiltrated skin when the disease relapsed after treatment. Other infiltration sites of lesions included bone marrow (2/5), peripheral blood (2/5), lymph nodes (3/5), liver and spleen (2/5). All patients had no clinical manifestation of central nervous system infiltration. Tumor cell specific immune markers CD4, CD56, CD123 were all positive, and the median Ki-67 index was 70%. TET2, ASXL1 and NRAS gene mutations were found respectively in 3 patients by next-generation sequencing technique (NGS). ALL-like, AML-like and invasive NK/T cell lymphoma-like first-line induction chemotherapy regimens were used for the patients. One patient died of severe complications during the early stage of chemotherapy, 3 patients were evaluated as CR, and 1 patient was evaluated as PR. 2 patients were recurred and progressed after induction of chemotherapy, and one of them was evaluated as CR after re-treatment. One patient received autologous hematopoietic stem cell transplantation (auto-HSCT) and got long-term survival (OS 87 months). 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which one died of transplantation related complications, and 2 cases survived. The median follow-up time of 4 patients with evaluable efficacy was 28.5(9-84) months, the median OS time was 31.5(10-87) months. CONCLUSION BPDCN is a highly heterogeneous malignant tumor with a poor prognosis. HSCT, especially allo-HSCT can significantly improve the prognosis of BPDCN patients.
Humans ; Male ; Female ; Adult ; Middle Aged ; Retrospective Studies ; Leukemia/pathology* ; Hematopoietic Stem Cell Transplantation ; Prognosis ; Myeloproliferative Disorders ; Skin Neoplasms/pathology* ; Acute Disease ; Dendritic Cells

Immunoglobulin (IgG) glycosylation affects the effector functions of IgG in a myriad of biological processes and has been closely associated with numerous autoimmune diseases, including systemic lupus erythematosus (SLE), thus underlining the pathogenic role of glycosylation aberration in autoimmunity. This study aims to explore the relationship between IgG sialylation patterns and lupus pregnancy. Relative to that in serum samples from the control cohort, IgG sialylation level was aberrantly downregulated in serum samples from the SLE cohort at four stages (from preconception to the third trimester of pregnancy) and was significantly associated with lupus activity and fetal loss during lupus pregnancy. The type I interferon signature of pregnant patients with SLE was negatively correlated with the level of IgG sialylation. The lack of sialylation dampened the ability of IgG to suppress the functions of plasmacytoid dendritic cells (pDCs). RNA-seq analysis further revealed that the expression of genes associated with the spleen tyrosine kinase (SYK) signaling pathway significantly differed between IgG- and deSia-IgG-treated pDCs. This finding was confirmed by the attenuation of the ability to phosphorylate SYK and BLNK in deSia-IgG. Finally, the coculture of pDCs isolated from pregnant patients with SLE with IgG/deSia-IgG demonstrated the sialylation-dependent anti-inflammatory function of IgG. Our findings suggested that IgG influences lupus activity through regulating pDCs function via the modulation of the SYK pathway in a sialic acid-dependent manner.
Humans ; Pregnancy ; Female ; Lupus Erythematosus, Systemic/pathology* ; Signal Transduction ; N-Acetylneuraminic Acid/metabolism* ; Immunoglobulin G ; Dendritic Cells/pathology*

OBJECTIVE: To investigate the efficacy and safety of chemotherapy combined with venetoclax followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN). METHODS: The clinical data of 3 patients with BPDCN undergoing allo-HSCT in Department of Hematology, Wuhan First Hospital from July 2017 to November 2021 were collected and retrospectively analyzed. RESULTS: Among the 3 patients, there were 1 male and 2 females, aged 27-52 years old. Skin lesions were observed during initial diagnosis, and it could also be characterized by acute leukemia. Characteristic molecular markers of tumor cells, such as CD4, CD56, CD123, and CD303 were positive. In addition, the expression detection of Bcl-2 in 3 patients were positive. Chemotherapy combined with venetoclax in the initial induction of chemotherapy (1 case) or disease recurrence and progress (2 cases) was performed. There were 2 cases evaluated as complete remission (CR) and 1 case as partial remission (PR) before allo-HSCT. The patients all received a nonmyeloablative conditioning without total body irradiation (TBI). The prevention programme of graft-versus-host disease (GVHD) was antithymocyte globulin + mycophenolate mofetil + cyclosporin A/FK506 ± methotrexate. The number of mononuclear cell (MNC) count was (16.73-18.35)×10⁸/kg, and CD34⁺ cell count was (3.57-4.65)×10⁶/kg. The 3 patients were evaluated as CR after allo-HSCT (+21 to +28 d), the donor-recipient chimerism rate was 100%, and Ⅲ-Ⅳ GVHD was not observed. One patient died at +50 d after transplantation, two patients were followed up for 28 months and 15 months, respectively, and achieved disease-free survival (DFS). CONCLUSIONS BPDCN is a highly aggressive malignant tumor with poor prognosis. Chemotherapy combined with venetoclax followed by allo-HSCT may lead to long-term DFS or even cure. Post-transplant maintenance is still unclear.
Female ; Humans ; Male ; Adult ; Middle Aged ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Acute Disease ; Graft vs Host Disease/prevention & control* ; Myeloproliferative Disorders ; Leukemia, Myeloid, Acute/pathology* ; Dendritic Cells

Cutaneous neurogenic inflammation (CNI) is inflammation that is induced (or enhanced) in the skin by the release of neuropeptides from sensory nerve endings. Clinical manifestations are mainly sensory and vascular disorders such as pruritus and erythema. Transient receptor potential vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1, respectively) are non-selective cation channels known to specifically participate in pain and CNI. Both TRPV1 and TRPA1 are co-expressed in a large subset of sensory nerves, where they integrate numerous noxious stimuli. It is now clear that the expression of both channels also extends far beyond the sensory nerves in the skin, occuring also in keratinocytes, mast cells, dendritic cells, and endothelial cells. In these non-neuronal cells, TRPV1 and TRPA1 also act as nociceptive sensors and potentiate the inflammatory process. This review discusses the role of TRPV1 and TRPA1 in the modulation of inflammatory genes that leads to or maintains CNI in sensory neurons and non-neuronal skin cells. In addition, this review provides a summary of current research on the intracellular sensitization pathways of both TRP channels by other endogenous inflammatory mediators that promote the self-maintenance of CNI.
Animals ; Chronic Disease ; Dendritic Cells ; metabolism ; pathology ; Dermatitis ; metabolism ; pathology ; Gene Expression Regulation ; Humans ; Inflammation ; metabolism ; pathology ; Keratinocytes ; metabolism ; pathology ; Mast Cells ; metabolism ; pathology ; Sensory Receptor Cells ; metabolism ; pathology ; TRPA1 Cation Channel ; biosynthesis ; TRPV Cation Channels ; biosynthesis

Immune thrombocytopenia (ITP) is recognized as a multifactorial cell-specific autoimmune disorder, and its pathogenesis is still not very clear. Traditional concept suggests that the platelet destruction mediated by autoantibodies is the pathophysiology mechanism of ITP, while many studies in recent years have shown that the abnormities of T lymphocyte, dendritic cell (DC), natural killer cell (NK), cytokine, programmed cell death (PCD), oxidative stress (OS), infection, pregnancy and drugs etc play an important role in the pathogenesis of ITP. Since the study of ITP has made a series of important achievements in recent years, this review focuses on the latest advance of studies on pathogenesis of ITP.
Apoptosis ; Autoantibodies ; blood ; Cytokines ; blood ; Dendritic Cells ; pathology ; Humans ; Killer Cells, Natural ; pathology ; Oxidative Stress ; Purpura, Thrombocytopenic, Idiopathic ; physiopathology ; T-Lymphocytes ; pathology

Dendritic Cells ; pathology ; Hematologic Neoplasms ; diagnosis ; therapy ; Humans

No abstract available.
Adult ; Antigens, CD4/*metabolism ; Antigens, CD56/*metabolism ; Bone Marrow/metabolism/pathology ; Dendritic Cells/cytology/*metabolism ; Diagnostic Errors ; Exons ; Female ; Flow Cytometry ; Gene Rearrangement ; Hematologic Neoplasms/diagnosis ; Histone-Lysine N-Methyltransferase/genetics ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Leukemia, Myeloid, Acute/*diagnosis ; Male ; Middle Aged ; Myeloid-Lymphoid Leukemia Protein/genetics ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; Transcription Factors/genetics ; Translocation, Genetic

Dendritic Cells ; pathology ; Humans ; Leukemia, Myeloid ; pathology ; Plasmacytoma ; pathology