15 research outputs found
New and simple equations to estimate the energy and fat contents and energy density of humans in sickness and health
Heterozygosity for Roquinsan leads to angioimmunoblastic T-cell lymphoma-like tumors in mice
Angioimmunoblastic T-cell lymphoma
(AITL) is the second most common peripheral
T-cell lymphoma with unusual clinical
and pathologic features and a poor
prognosis despite intensive chemotherapy.
Recent studies have suggested
AITL derives from follicular helper T (TFH)
cells, but the causative molecular pathways
remain largely unknown. Here we
show that approximately 50% of mice
heterozygous for the “san” allele of
Roquin develop tumors accompanied by
hypergammaglobulinemia by 6 months of
age. Affected lymph nodes displayed the
histologic features diagnostic of AITL,
except for the presence of expanded FDC
networks. Accumulation of TFH cells preceded
tumor development, and clonal rearrangements
in the TCR-B genes were
present in most tumors. Furthermore, TFH
cells exhibited increased clonality compared
with non-TFH cells from the same
lymph nodes, even in the absence of
tumors. Genetic manipulations that prevent
TFH development, such as deletion of
ICOS, CD28, and SAP, partially or completely
abrogated tumor development,
confirming a TFH-derived origin. Roquinsan/+
mice emerge as a useful model to investigate
the molecular pathogenesis of AITL
and for preclinical testing of therapies
aimed at targeting dysregulated TFH cells
or their consequences.This work was supported by a Viertel Senior Medical Research
Fellowship and National Health and Medical Research Council
program and project grants (C.G.V.) and a National Health and
Medical Research Council Overseas Biomedical Fellowship (J.I.E.)