Dataset Information

Structural and diffusion weighted MRI demonstrates responses to ibrutinib in a mouse model of follicular helper (Tfh) T-cell lymphoma.

ABSTRACT: Recent analyses of the genetics of peripheral T-cell lymphoma (PTCL) have shown that a large proportion of cases are derived from normal follicular helper (Tfh) T-cells. The sanroque mouse strain bears a mutation that increases Tfh cell number and heterozygous animals (Roquinsan/+) develop lymphomas similar to human Tfh lymphoma. Here we demonstrate the usefulness of Roquinsan/+ animals as a pre-clinical model of Tfh lymphoma. Long latency of development and incomplete penetrance in this strain suggests the lymphomas are genetically diverse. We carried out preliminary genetic characterisation by whole exome sequencing and detected tumor specific mutations in Hsp90ab1, Ccnb3 and RhoA. Interleukin-2-inducible kinase (ITK) is expressed in Tfh lymphoma and is a potential therapeutic agent. A preclinical study of ibrutinib, a small molecule inhibitor of mouse and human ITK, in established lymphoma was carried out and showed lymphoma regression in 8/12 (67%) mice. Using T2-weighted MRI to assess lymph node volume and diffusion weighted MRI scanning as a measure of function, we showed that treatment increased mean apparent diffusion coefficient (ADC) suggesting cell death, and that change in ADC following treatment correlated with change in lymphoma volume. We suggest that heterozygous sanroque mice are a useful model of Tfh cell derived lymphomas in an immunocompetent animal.

SUBMITTER: Allchin RL

PROVIDER: S-EPMC6478326 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Structural and diffusion weighted MRI demonstrates responses to ibrutinib in a mouse model of follicular helper (Tfh) T-cell lymphoma.

Allchin Rebecca L RL Kelly Michael E ME Mamand Sami S Doran Anthony G AG Keane Thomas T Ahearne Matthew J MJ Wagner Simon D SD

PloS one 20190423 4

Recent analyses of the genetics of peripheral T-cell lymphoma (PTCL) have shown that a large proportion of cases are derived from normal follicular helper (Tfh) T-cells. The sanroque mouse strain bears a mutation that increases Tfh cell number and heterozygous animals (Roquinsan/+) develop lymphomas similar to human Tfh lymphoma. Here we demonstrate the usefulness of Roquinsan/+ animals as a pre-clinical model of Tfh lymphoma. Long latency of development and incomplete penetrance in this strain ...[more]

PMID: 31013298

Similar Datasets

Project description:Diffusion weighted imaging (DWI) constitutes a major functional parameter performed in Magnetic Resonance Imaging (MRI). The DW sequence is performed by acquiring a set of native images described by their b-values, each b-value representing the strength of the diffusion MR gradients specific to that sequence. By fitting the data with models describing the motion of water in tissue, an apparent diffusion coefficient (ADC) map is built and allows the assessment of water mobility inside the tissue. The high cellularity of tumors restricts the water diffusion and decreases the value of ADC within tumors, which makes them appear hypointense on ADC maps. The role of this sequence now largely exceeds its first clinical apparitions in neuroimaging, whereby the method helped diagnose the early phases of cerebral ischemic stroke. The applications extend to whole-body imaging for both neoplastic and non-neoplastic diseases. This review emphasizes the integration of DWI in the genitourinary system imaging by outlining the sequence's usage in female pelvis, prostate, bladder, penis, testis and kidney MRI. In gynecologic imaging, DWI is an essential sequence for the characterization of cervix tumors and endometrial carcinomas, as well as to differentiate between leiomyosarcoma and benign leiomyoma of the uterus. In ovarian epithelial neoplasms, DWI provides key information for the characterization of solid components in heterogeneous complex ovarian masses. In prostate imaging, DWI became an essential part of multi-parametric Magnetic Resonance Imaging (mpMRI) to detect prostate cancer. The Prostate Imaging-Reporting and Data System (PI-RADS) scoring the probability of significant prostate tumors has significantly contributed to this success. Its contribution has established mpMRI as a mandatory examination for the planning of prostate biopsies and radical prostatectomy. Following a similar approach, DWI was included in multiparametric protocols for the bladder and the testis. In renal imaging, DWI is not able to robustly differentiate between malignant and benign renal tumors but may be helpful to characterize tumor subtypes, including clear-cell and non-clear-cell renal carcinomas or low-fat angiomyolipomas. One of the most promising developments of renal DWI is the estimation of renal fibrosis in chronic kidney disease (CKD) patients. In conclusion, DWI constitutes a major advancement in genitourinary imaging with a central role in decision algorithms in the female pelvis and prostate cancer, now allowing promising applications in renal imaging or in the bladder and testicular mpMRI.

Dataset Information

Structural and diffusion weighted MRI demonstrates responses to ibrutinib in a mouse model of follicular helper (Tfh) T-cell lymphoma.

Publications

Structural and diffusion weighted MRI demonstrates responses to ibrutinib in a mouse model of follicular helper (Tfh) T-cell lymphoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets