Cell-type-specific sensitivity of bortezomib in the methotrexate-resistant primary central nervous system lymphoma cells

Abstract Background Primary central nervous system lymphoma (PCNSL), a relatively rare brain tumor, bears a dire prognosis. On occasion, rapid progression of the tumor makes immediate diagnosis and initiation of therapy imperative. To achieve swift diagnosis, we adopt flow cytometry (FCM) in addition to conventional histopathology. The aim of this study is to reveal utility and drawbacks of FCM diagnosis for PCNSL. Methods Patients with suspected PCNSL on neuroradiological findings and received both FCM and histological diagnosis between August 2015 and April 2020 were retrospectively enrolled into the study. Tumor samples were collected by craniotomy with either of endoscope or microscope. The patients’ electronic medical records were investigated, and histological findings, results of FCM, and other clinical data were evaluated. Results Twenty seven patients met the eligibility criteria. Twenty three patients (11 males and 12 females) were diagnosed with PCNSL by histological confirmation, and 22 cases were B-cell type lymphoma and 1 was T-cell type. Median age at diagnosis was 65. FCM analysis showed lymphoma pattern in 20 cases, but in the other 3 lymphoma cases (FCM discordant: FCM-D) and 4 non-lymphomatous tumor cases, FCM results did not show lymphoma pattern (sensitivity: 86.4%, specificity: 100%). Analysis of FCM-D cases showed infiltration of T lymphocytes or astrocytes into the tumor tissue, indicating tumor microenvironmental reaction, were observed, and it is assumed that those reactions deceived FCM diagnosis. Conclusions Despite some disadvantages, diagnosis of PCNSL by FCM is rapid and reliable.

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A developmentally regulated DNA-binding protein from mouse brain stimulates myelin basic protein gene expression

Molecular and Cellular Biology ◽

10.1128/mcb.13.5.3103-3112.1993 ◽

1993 ◽

Vol 13 (5) ◽

pp. 3103-3112

Author(s):

S Haas ◽

J Gordon ◽

K Khalili

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Dna Binding ◽

Myelin Basic Protein ◽

Mouse Brain ◽

Basic Protein ◽

Binding Protein ◽

Cell Type ◽

A Cell ◽

Cell Type Specific

Transcription of the myelin basic protein (MBP) gene is regulated in a cell-type-specific and developmental stage-specific manner during myelin formation in the murine central nervous system. The 5'-flanking region of the MBP gene contains several regulatory elements that differentially contribute to the cell-type-specific transcription of MBP in cells derived from the central nervous system. The proximal element, termed MB1, which is located between nucleotides -14 and -50 with respect to the RNA start site, has previously been shown to have characteristics of a cell-type-specific enhancer element. In this study, we used band shift and UV cross-linking assays to identify DNA-binding proteins in mouse brain nuclear extract which interact with the MB1 element. Fractionation of these extracts has allowed the identification of a 38- to 41-kDa nuclear protein, derived from mouse brain tissue at the peak of myelination, which specifically binds the MB1 DNA sequence. Fractions enriched in the MB1-binding protein have been shown to stimulate transcription of the MBP promoter in extract derived from HeLa cells. MB1 binding protein activity is expressed in a tissue-specific and development stage-specific pattern which coincides with the pattern of MBP transcription, suggesting that this protein may be a biologically relevant transcription factor for the MBP gene in vivo.

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