Marion Haas

Bio: Marion Haas is an academic researcher from University of Rennes. The author has contributed to research in topics: Interleukin 4 & Naive B cell. The author has an hindex of 1, co-authored 2 publications receiving 7 citations.

Discordant Response of Systemic Mastocytosis Associated With Myelodysplastic Syndrome After Midostaurin and Allogeneic Hematopoietic Stem-cell Transplantation.

Abstract: Systemic mastocytosis (SM) is a rare and heterogeneous disease characterized by the accumulation of neoplastic mast cells in various tissues, predominantly skin and bone marrow (BM). Thirty percent of SM is associated with a hematological neoplasm, referred to as SM-AHN, which confers a poor prognosis. The somatic KIT D816V mutation is a diagnostic hallmark of SM and the major therapeutic target in advanced mastocytosis. Here, we report the case of a patient with an SM associated with a myelodysplastic syndrome (MDS) who achieved discordant responses after midostaurin and allogenic hematopoietic stem cell transplantation (HSCT). We performed serial high throughput sequencing (HTS) to evaluate the responses after each line of treatment and to guide therapeutic decision making. Through these monitoring, we investigated the clonal evolution of this complex disease. A 59-year-old woman was referred to our Hematology department for night sweats, asthenia, weight loss, and a voluminous splenomegaly of 15 cm below the costal margin. Complete blood cell count revealed a pancytopenia (hemoglobin 7.6g/dL, platelets 60 10/L leukocytes 1.8 10/L with 0.6 10/L neutrophils) (Table 1-M0). The BM aspirate smear showed marked myelodysplastic changes in erythroid and granulocytic lineages, no ring sideroblasts, less than 5% of blasts and the presence of mast cells with abnormal cytological features: hypogranularity, oval eccentric nucleus, and spindle shape morphology (Fig. 1A). Mast cells showed a strong expression of CD25 and CD2 by flow cytometry. The BMbiopsy was infiltrated

STAT6: A review of a signaling pathway implicated in various diseases with a special emphasis in its usefulness in pathology.

Abstract: Signal Transducer and Activator of Transcription 6 (STAT6), belonging to a family of seven similar members is primarily stimulated by interleukin(IL)-4 and IL-13, and acts as a T helper type 2 (Th2)-inducing factor. Thus, it is implicated in the pathophysiology of various allergic conditions, such as asthma, atopic dermatitis, eosinophilic esophagitis and food allergies, but also in tumor microenvironment regulation. Furthermore, certain forms of lymphomas, notably the Hodgkin lymphoma group, the primary mediastinal and primary central nervous system lymphoma, as well as some follicular and T cell lymphomas are associated with dysregulation of the STAT6 pathway. STAT6 immunohistochemical expression also serves as a surrogate marker in the diagnosis of solitary fibrous tumor, despite not directly responsible for the tumorigenic effect. These pathophysiological implications of the STAT6 pathway, its diagnostic or prognostic role in pathology, as well its immunohistochemical detection with different antibodies will be discussed in this review.

Identification of Potential Key Genes and Regulatory Markers in Essential Thrombocythemia Through Integrated Bioinformatics Analysis and Clinical Validation

Abstract: Introduction Essential thrombocytosis (ET) is a group of myeloproliferative neoplasms characterized by abnormal proliferation of platelet and megakaryocytes. Research on potential key genes and novel regulatory markers in essential thrombocythemia (ET) is still limited. Methods Downloading array profiles from the Gene Expression Omnibus database, we identified the differentially expressed genes (DEGs) through comprehensive bioinformatic analysis. GO, and REACTOME pathway enrichment analysis was used to predict the potential functions of DEGs. Besides, constructing a protein-protein interaction (PPI) network through the STRING database, we validated the expression level of hub genes in an independent cohort of ET, and the transcription factors (TFs) were detected in the regulatory networks of TFs and DEGs. And the candidate drugs that are targeting hub genes were identified using the DGIdb database. Results We identified 63 overlap DEGs that included 21 common up-regulated and 42 common down-regulated genes from two datasets. Functional enrichment analysis shows that the DEGs are mainly enriched in the immune system and inflammatory processes. Through PPI network analysis, ACTB, PTPRC, ACTR2, FYB, STAT1, ETS1, IL7R, IKZF1, FGL2, and CTSS were selected as hub genes. Interestingly, we found that the dysregulated hub genes are also aberrantly expressed in a bone marrow cohort of ET. Moreover, we found that the expression of CTSS, FGL2, IKZF1, STAT1, FYB, ACTR2, PTPRC, and ACTB genes were significantly under-expressed in ET (P<0.05), which is consistent with our bioinformatics analysis. The ROC curve analysis also shows that these hub genes have good diagnostic value. Besides, we identified 4 TFs (SPI1, IRF4, SRF, and AR) as master transcriptional regulators that were associated with regulating the DEGs in ET. Cyclophosphamide, prednisone, fluorouracil, ruxolitinib, and lenalidomide were predicted as potential candidate drugs for the treatment of ET. Discussion These dysregulated genes and predicted key regulators had a significant relationship with the occurrence of ET with affecting the immune system and inflammation of the processes. Some of the immunomodulatory drugs have potential value by targeting ACTB, PTPRC, IL7R, and IKZF1 genes in the treatment of ET.