Mature lymphoid malignancies: origin, stem cells, and chronicity

Abstract

The chronic behavior of mature lymphoid malignancies, with relapses occurring years apart in many patients, has until recently been unexplained. Patterns of relapse also differ vastly between disease entities, with some being highly curable by chemotherapy whereas others are destined to reemerge after treatment. Lately, the use of next-generation sequencing techniques has revealed essential information on the clonal evolution of lymphoid malignancies. Also, experimental xenograft transplantation point to the possible existence of an ancestral (stem) cell. Such a malignant lymphoid stem cell population could potentially evade current therapies and be the cause of chronicity and death in lymphoma patients; however, the evidence is divergent across disease entities and between studies. In this review we present an overview of genetic studies, case reports, and experimental evidence of the source of mature lymphoid malignancy and discuss the perspectives.

Existence of reprogrammed lymphoma stem cells in a murine ALCL-like model

“…The existence of lymphoma stem cells is supported by several case stories, in which both -recipient and donordevelop the same lymphoid disease after allogeneic transplant. Genetic sequence homology proved the same origin of the recipient and donor tumors [35]. Our data identify a distinct lymphoma stem cell population, which displays ambiguous features: while these lymphoma stem cells show immunophenotypical features of DN3/DN4 cells, gene expression profiles resemble primitive stem-cell-like features.…”

Effect of transplantation of cardiac stem cells overexpressing integrin‑linked kinase on cardiac function of rats with acute myocardial infarction

“…Traditional treatment methods, such as percutaneous transluminal coronary angioplasty, myocardial reperfusion therapy or coronary artery bypass grafting, can improve patients' cardiac function to some extent, but the prognosis is poor ( 5 ). CSCs have superior performance of directional differentiation, which can be directionally differentiated into myocardial cells, providing a new choice for cardiac cell transplantation therapy after MI ( 8 ). Zhong and Rao ( 18 ) studied and showed that after the treatment of ischemic cardiomyopathy with CSC transplantation therapy, the migration and proliferation capabilities of CSCs are superior, there are many new cells and blood vessels in the MI region, and cardiac function recovery is better.…”

“…Poulos ( 7 )studied and showed that stem cell transplantation can promote the regeneration of myocardial cells in the local infarct region, thereby repairing the heart and improving the cardiac function. At present, the main stem cells applied include bone marrow mesenchymal, hematopoietic, embryonic and cardiac stem cells (CSCs) ( 8 – 11 ), among which CSC, with strong proliferation and differentiation capacities, is an innate undifferentiated cell derived from the heart ( 12 ). CSCs possess the regenerative potential and appear in the myocardial ischemic region in animal model experiment, which can be directionally differentiated into myocardial, vascular smooth muscle and vascular endothelial cells and fibroblasts, thereby participating in repairing the cardiac function ( 5 , 9 ).…”

Forward and Reverse Genetics of B Cell Malignancies: From Insertional Mutagenesis to CRISPR-Cas

“…B cell neoplasms can be categorized by their cell of origin, each subtype being representative of a discrete stage in differentiation with characteristic phenotypes and genetic lesions (Table 1, Figure 1) [reviewed in (1,2)]. Accurate modelling of these diseases in mice requires alteration of various biological processes at different stages of B cell development including differentiation, migration, rearrangement of immunoglobulin genes, T helper interactions, positive selection for antigen and negative selection against autoreactivity.…”

“…Speculation on the developmental stage that each malignancy is derived from is based on a combination of genetic lesions and phenotypic characteristics [reviewed in (1,2)]. The cell of origin suggested by translocation breakpoints does not always match the cell of origin suggested by somatic hypermutations and/or markers expressed on the cell surface.…”