Coordinated Silencing of MYC-Mediated miR-29 by HDAC3 and EZH2 as a Therapeutic Target of Histone Modification in Aggressive B-Cell Lymphomas

We investigated the transcriptional and epigenetic repression of miR-29 by MYC, HDAC3, and EZH2 in mantle cell lymphoma and other MYC-associated lymphomas. We demonstrate that miR-29 is repressed by MYC through a corepressor complex with HDAC3 and EZH2. MYC contributes to EZH2 upregulation via repression of the EZH2 targeting miR-26a, and EZH2 induces MYC via inhibition of the MYC targeting miR-494 to create positive feedback. Combined inhibition of HDAC3 and EZH2 cooperatively disrupted the MYC-EZH2-miR-29 axis, resulting in restoration of miR-29 expression, downregulation of miR-29-targeted genes, and lymphoma growth suppression in vitro and in vivo. These findings define a MYC-mediated miRNA repression mechanism, shed light on MYC lymphomagenesis mechanisms, and reveal promising therapeutic targets for aggressive B-cell malignancies

PHENYTOIN-ASSOCIATED LYMPHOADENOPATHY MIMICKING A PERIPHERAL T-CELL LYMPHOMA

<span style="font-size: 12.0pt; font-family: " lang="EN-US">We report a case of phenytoin-induced pseudolymphoma in a 28-year-old male with a history of autism and seizure disorder.<span style="mso-spacerun: yes;">  </span>The patient presented with bilateral cervical lymphadenopathy that was shown to be moderately to markedly FDG-avid on a whole body PET/CT scan.<span style="mso-spacerun: yes;">  </span>Flow cytometry analysis of peripheral blood and bone marrow mononuclear cells detected identical T cell population with aberrant immunophenotype.<span style="mso-spacerun: yes;">  </span>Additionally,<span style="background: white;"> a TCR beta gene was found to be clonally rearranged in both peripheral blood and bone marrow supporting a clonal origin of atypical T cells. However, </span>no such clonal population of T-cells could be detected in a pathologic specimen obtained from an excisional biopsy of one of the patient’s cervical lymph nodes. After discontinuing the patient’s phenytoin, his lymphadenopathy has nearly completely resolved and circulation clonal T cell population disappeared with 12 months of follow-up.<br style="mso-special-character: line-break; page-break-before: always;" /></span&gt

Review and Updates on Systemic Mastocytosis and Related Entities

Mast cell disorders range from benign proliferations to systemic diseases that cause anaphylaxis and other diverse symptoms to mast cell neoplasms with varied clinical outcomes. Mastocytosis is the pathologic process of the accumulation of abnormal mast cells in different organs, mostly driven by KIT mutations, and can present as cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma. The WHO 5th edition classification divides systemic mastocytosis into bone marrow mastocytosis, indolent systemic mastocytosis, smoldering systemic mastocytosis, aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast cell leukemia. The new ICC classifies SM slightly differently. The diagnosis of SM requires the integration of bone marrow morphologic, immunophenotypic, and molecular findings, as well as clinical signs and symptoms. Moreover, understanding the wide range of clinical presentations for patients with mast cell disorders is necessary for accurate and timely diagnosis. This review provides an updated overview of mast cell disorders, with a special emphasis on SM, including the latest approaches to diagnosis, prognostic stratification, and management of this rare disease