Adult high-grade B-cell lymphoma with Burkitt lymphoma signature: genomic features and potential therapeutic targets.
نویسندگان
چکیده
The adult high-grade B-cell lymphomas sharing molecular features with Burkitt lymphoma (BL) are highly aggressive lymphomas with poor clinical outcome. High-resolution structural and functional genomic analysis of adult Burkitt lymphoma (BL) and high-grade B-cell lymphoma with BL gene signature (adult-molecularly defined BL [mBL]) revealed the MYC-ARF-p53 axis as the primary deregulated pathway. Adult-mBL had either unique or more frequent genomic aberrations (del13q14, del17p, gain8q24, and gain18q21) compared with pediatric-mBL, but shared commonly mutated genes. Mutations in genes promoting the tonic B-cell receptor (BCR)→PI3K pathway (TCF3 and ID3) did not differ by age, whereas effectors of chronic BCR→NF-κB signaling were associated with adult-mBL. A subset of adult-mBL had BCL2 translocation and mutation and elevated BCL2 mRNA and protein expression, but had a mutation profile similar to mBL. These double-hit lymphomas may have arisen from a tumor precursor that acquired both BCL2 and MYC translocations and/or KMT2D (MLL2) mutation. Gain/amplification of MIR17HG and its paralogue loci was observed in 50% of adult-mBL. In vitro studies suggested miR-17∼92's role in constitutive activation of BCR signaling and sensitivity to ibrutinib. Overall integrative analysis identified an interrelated gene network affected by copy number and mutation, leading to disruption of the p53 pathway and the BCR→PI3K or NF-κB activation, which can be further exploited in vivo by small-molecule inhibitors for effective therapy in adult-mBL.
منابع مشابه
Role of Stem Cell Transplantation in the Treatment of Burkitt Lymphoma; A Systematic Review
Background: Burkitt lymphoma is a common subtype of non-Hodgkin lymphoma in children. It has a rapid and aggressive clinical course with frequent involvement of bone marrow and central nervous system. Systemic chemotherapy is the mainstay of the treatment for this malignancy in children. In this systematic review, we discuss autologous and allogeneic hematopoietic stem cell transplantation (HSC...
متن کاملA Case Report of a Metastatic Primary Gastric Lymphoma; Diffuse Large B-Cell or Burkitt Lymphoma?
Introduction: Primary gastric lymphoma (PGL) is a rare tumor, whose differential diagnosis may become complicated without precise immunohistochemistry (IHC) and genetic analysis. Case Presentation: A 33-year-old woman presented with gastric cancer and had undergone gastrectomy without precise IHC and staging in another center. Inappropriate IHC after surgery showed diffuse large B-cell lymphom...
متن کاملA Case Report of a Metastatic Primary Gastric Lymphoma; Diffuse Large B-Cell or Burkitt Lymphoma?
Introduction: Primary gastric lymphoma (PGL) is a rare tumor, whose differential diagnosis may become complicated without precise immunohistochemistry (IHC) and genetic analysis. Case Presentation: A 33-year-old woman presented with gastric cancer and had undergone gastrectomy without precise IHC and staging in another center. Inappropriate IHC after surgery showed diffuse large B-cell lymphom...
متن کاملLarge B-cell lymphoma in a dog: A cyto-histopathological evaluation and Immunophenotyping according to WHO classification for canine lymphomas
In the present study, we described cyto-histopathological features and immunophenotyping of the large B-cell lymphoma in an 8-year-old mixed breed dog with applying the World Health Organization (WHO) system of classification of canine lymphomas. In fine-needle aspiration (FNA), lymph nodes were involved by neoplastic cells of intermediate to large size with deep blue cytoplasm; consist of cent...
متن کاملAdult Burkitt leukemia and lymphoma.
The World Health Organization Classification of Lymphoid Neoplasms identifies Burkitt lymphoma/leukemia as a highly aggressive mature B-cell neoplasm consisting of endemic, sporadic, and immunodeficiency-associated variants. These subtypes share many morphologic and immunophenotypic features, but differences exist in their clinical and geographic presentations. All of these subtypes possess chr...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Blood
دوره 130 16 شماره
صفحات -
تاریخ انتشار 2017