Browsing by Author "Dave, Sandeep"

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Open Access
Molecular characteristics of mantle cell lymphoma presenting with clonal plasma cell component.
(The American journal of surgical pathology, 2011-02) Visco, Carlo; Hoeller, Sylvia; Malik, Jeffrey T; Xu-Monette, Zijun Y; Wiggins, Michele L; Liu, Jessica; Sanger, Warren G; Liu, Zhongfeng; Chang, Julie; Ranheim, Erik A; Gradowski, Joel F; Serrano, Sergio; Wang, Huan-You; Liu, Qingquan; Dave, Sandeep; Olsen, Brian; Gascoyne, Randy D; Campo, Elias; Swerdlow, Steven H; Chan, Wing C; Tzankov, Alexander; Young, Ken H
The normal counterparts of mantle cell lymphoma (MCL) are naive, quiescent B cells that have not been processed through the germinal center (GC). For this reason, although lymphomas arising from GC or post-GC B cells often exhibit plasmacytic differentiation, MCL rarely presents with plasmacytic features. Seven cases of MCL with a monotypic plasma cell (PC) population were collected from 6 centers and were studied by immunohistochemistry, fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms analysis, capillary gel electrophoresis, and restriction fragment length polymorphism of immunoglobulin heavy chain analysis of microdissections of each of the MCL and PC populations to assess their clonal relationship. The clinical presentation was rather unusual compared with typical MCL, with 2 cases arising from the extranodal soft tissues of the head. All MCL cases were morphologically and immunohistochemically typical, bearing the t(11;14)(q13;q32). In all cases, the PC population was clonal. In 5 of the 7 cases, the MCL and PC clones showed identical restriction fragments, indicating a common clonal origin of the neoplastic population. The 2 cases with clonal diversity denoted the coexistence of 2 different tumors in a composite lymphoma/PC neoplasm. Our findings suggest that MCL can present with a PC component that is often clonally related to the lymphoma, representing a rare but unique biological variant of this tumor.
Embargo
Profiling the Molecular Determinants of Origin and Response in Blood Cancers
(2024) Thakkar, Devang
Blood cancers are among the most common types of malignancies. Over 175,000 new cases of blood cancers representing over one hundred distinct malignancies were diagnosed in the United States in 2023. Understanding the molecular determinants underlying the origin of these malignancies and their response to treatment is essential to improving diagnostic accuracy and identifying the most promising therapeutic options for patients. This dissertation aims to determine molecular profiles associated with treatment response and normal cell of origin using data drawn from the landscape of genetic alterations in blood cancers.
Diffuse large B cell lymphoma (DLBCL) is the most common form of blood cancer with over 18,000 new cases diagnosed every year in the United States. The treatment for DLBCL has remained unchanged for over two decades, and a large subset of patients are refractory to treatment or relapse after initial response. Patients with relapsed/refractory disease (rrDLBCL) have a dismal prognosis. The approval of chimeric antigen receptor T-cell (CAR-T) therapy has greatly improved the odds of survival for these patients. However, not all patients treated with CAR-T therapy experience prolonged remission. In Chapter 2, I describe my work towards understanding the genetic determinants of response in a real-world dataset of patients treated with CAR-T therapy, identifying clinical factors and gene expression signatures relevant to prognosis after treatment.
Genomic profiling efforts for blood cancers have thus far been limited to the most common entities, and the heterogeneity in processing and methods between these studies hinders comparison between different malignancies. In Chapter 3, I describe my work on the Atlas of Blood Cancer Genomes (ABCG) project, a comprehensive profiling study of all blood cancers described in the World Health Organization classification. In the first half of this chapter, I describe the design and development of tools and methods to explore the genomic landscape of blood cancers. In the second half of this chapter, I highlight the application of these methods to three distinct blood cancers – primary mediastinal B cell lymphoma, extranodal marginal zone lymphoma, and blastic plasmacytoid dendritic cell neoplasm – with very different molecular and clinical features that highlight the diversity of blood cancers.
A tumor cell often closely resembles the normal cell it originates from in terms of its gene expression profiles, surface marker expression and cellular behavior. As a result, surface markers from normal cells are commonly used to diagnose cancers using flow cytometry. However, the normal cell of origin for some blood cancers such as marginal zone lymphoma (MZL) has not been comprehensively characterized. In Chapter 4, I discuss the work I performed to determine the cell of origin of MZL, highlighting two potential subsets of MZL and their putative cells of origin.
Overall, this dissertation explores how an understanding of the genetics of blood cancers can address fundamental questions related to their origin, characterization, and response to treatment.