Progression and Transformation of Clonally Heterogeneous B-cell Lymphoma

Indolent B- cell non-Hodgkin lymphoma can transform into aggressive lymphoma. We extend our prior mathematical model to analyze and predict transformation. To provide additional confidence in our model, we compare it with SCID mouse data for combination therapy of Diffuse Large B-cell Lymphoma, an a...

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Bibliographic Details
Published in:PloS one 2015-06, Vol.10 (6), p.e0130590-e0130590
Main Authors: Weiss, Robert F, Smith, Mitchell R, Miller, Merlin G, Cronin, John F
Format: Article
Language:English
Subjects:
Analysis
Aniline Compounds - pharmacology
Aniline Compounds - therapeutic use
Animals
Apoptosis
B-cell lymphoma
Birth rate
Cancer
Cell death
Cell Transformation, Neoplastic - drug effects
Cell Transformation, Neoplastic - pathology
Clone Cells
Cloning
Development and progression
Disease Progression
Drug dosages
Experiments
Health aspects
Hypotheses
Immune response
Immune system
Immunity - drug effects
Leukemia
Lymphocytes B
Lymphoma
Lymphoma, Large B-Cell, Diffuse - drug therapy
Lymphoma, Large B-Cell, Diffuse - immunology
Lymphoma, Large B-Cell, Diffuse - pathology
Mathematical models
Mice, SCID
Models, Biological
Mutation
Non-Hodgkin's lymphomas
Rituximab - pharmacology
Rituximab - therapeutic use
Scaling
Sulfonamides - pharmacology
Sulfonamides - therapeutic use
Time Factors
Transformation
Tumors
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Description
Summary:Indolent B- cell non-Hodgkin lymphoma can transform into aggressive lymphoma. We extend our prior mathematical model to analyze and predict transformation. To provide additional confidence in our model, we compare it with SCID mouse data for combination therapy of Diffuse Large B-cell Lymphoma, an aggressive form of the disease. We develop a two cell model that includes indolent and aggressive clones but no immune response and use it to predict transformation. An approximate model for the time to transformation is derived that provides insight regarding scaling effects. We then add an immune response and therapeutic measures, and illustrate the complex interactions among the various processes, with a focus on transformation. The implications for initial diagnosis and treatment of non-Hodgkin lymphoma are discussed.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0130590