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Spontaneous regression is a recognized phenomenon in chronic lymphocytic leukemia (CLL) but its biological basis remains unknown. We undertook a detailed investigation of the biological and clinical features of 20 spontaneous CLL regression cases incorporating phenotypic, functional, transcriptomic and genomic studies at sequential timepoints. All spontaneously regressed tumors were IGHV-mutated with no restricted IGHV usage or B-cell receptor (BCR) stereotypy. They exhibited shortened telomeres similar to non-regressing CLL indicating prior proliferation. They also displayed low Ki-67, CD49d, sIgM expression and IgM signaling response but high CXCR4 expression indicating low proliferative activity associated with poor migration to proliferation centers, with these features becoming increasingly marked during regression. Spontaneously regressed CLL displayed a transcriptome profile characterized by downregulation of metabolic processes as well as MYC and its downstream targets compared to non-regressing CLL. Moreover, spontaneous regression was associated with reversal of T-cell exhaustion features including reduced PD-1 expression and increased T-cell proliferation. Interestingly, archetypal CLL genomic aberrations including HIST1H1B and TP53 mutations and del(13q14) were found in some spontaneously regressing tumors, but genetic composition remained stable during regression. Conversely, a single case of CLL relapse following spontaneous regression was associated with increased BCR signaling, CLL proliferation and clonal evolution. These observations indicate that spontaneously regressing CLL appear to undergo a period of proliferation before entering a more quiescent state, and that a complex interaction between genomic alterations and microenvironment determines disease course. Together, the findings provide novel insight into the biological processes underpinning spontaneous CLL regression, with implications for CLL treatment.
This article was published in the following journal.
Spontaneous regression in intracranial germ cell tumors (GCTs) is an extremely rare phenomenon with only 9 cases been reported. The mechanism and nature history of this phenomenon are still equivocal.
Spontaneous regression of cystic adventitial disease of the popliteal artery is rare. In this report, we describe a 54-year-old woman who presented with left calf pain and was diagnosed with cystic ad...
Spontaneous regression of a malignant tumor is defined as "the partial or complete disappearance of a malignant tumor in the absence of any treatment." Herein, we report a case of occult breast cancer...
The natural history of sporadic vestibular schwannoma is unpredictable, with tumors growing, non-growing and even showing spontaneous regression in some rare cases.
Developmental regression occurs in approximately one-third of children with autism spectrum disorder (ASD). There is a strong genetic influence in ASD and hundreds of genes have been implicated. Theor...
The purpose is to develop a registry-based biobank for integrative physiological analysis based on biological samples (blood, urine, interstitial fluid and muscle) from subjects enrolled i...
This study will investigate the utility of integrative sequencing of individuals and families at risk of hereditary cancer syndromes and will uncover novel contributors to tumourigenesis. ...
Integrative analysis of GBM
Spontaneous Coronary Artery Dissection (SCAD) is a rare and often misdiagnosed cause of Acute Coronary Syndrome (ACS) affecting predominantly young women without cardiovascular risk factor...
The purpose of this study is to analyze the gene expression patterns associated with various microenvironmental stresses in tumors to understand their roles in tumor progression and treatm...
Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see LINEAR MODELS) the relationship is constrained to be a straight line and LEAST-SQUARES ANALYSIS is used to determine the best fit. In logistic regression (see LOGISTIC MODELS) the dependent variable is qualitative rather than continuously variable and LIKELIHOOD FUNCTIONS are used to find the best relationship. In multiple regression, the dependent variable is considered to depend on more than a single independent variable.
Methods used to take into account and incorporate spatial autocorrelation and regional variation into regression analysis models of data that has spatial dependency, and also to provide information on the spatial relationships among the variables.
A statistical analytic technique used with discrete dependent variables, concerned with separating sets of observed values and allocating new values. It is sometimes used instead of regression analysis.
Disappearance of a neoplasm or neoplastic state without the intervention of therapy.
Tumors most commonly seen on or near the genitalia. They are venereal, most likely transmitted through transplantation of cells by contact. Metastases have been reported. Spontaneous regression may occur.
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...