8 research outputs found
Chronic lymphocytic leukemia cells in lymph nodes show frequent NOTCH1 activation
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western world. Pathogenic mechanisms involve multiple external events (such as microenvironmental and antigenic stimuli) and internal events (genetic and epigenetic alterations) that are associated with the transformation, progression and evolution of CLL. CLL is characterized by an accumulation of mature B cells in peripheral blood, bone marrow and lymphoid tissues. Extracellular stimuli play an important role in the development and maintenance of neoplastic cells. B-CLL cells proliferate and activate pathogenic signaling pathways in anatomical structures known as proliferation centers, which are usually more conspicuous in involved lymph nodes.1 Its clinical course is quite heterogeneous, whereby some patients progress rapidly and have short survival, whereas others have a more stable clinical course that may not need treatment for years.This work was supported by grants from the Ministerio de Economía y Competitividad (MINECO) (SAF2013-47416-R) Instituto de Salud Carlos III (ISCIII)- FEDER – MINECO- AES (CP11/00018, PI10/00621, RD012/0036/0060), and Asociación Española contra el Cancer (AECC). MS-B is supported by a Miguel Servet contract from ISCIII-FEDER (CP11/00018). Salary support to SG is provided by CP11/00018, from ISCIII-FEDER. JG-R is supported by a predoctoral grant from the Fundación Investigación Puerta de Hierro.S
Recurrent presence of the PLCG1 S345F mutation in nodal peripheral T-cell lymphomas
This work was supported by grants from Asociación
Española contra el Cancer (AECC), Ministerio de Economía y
Competitividad (MINECO) (SAF2013-47416-R), Instituto Salud
Carlos III (ISCIII) – Fondos FEDER, MINECO-AES(RD012/0036/0060, PI10/00621, CP11/00018). RM is supported
by the Fundación Conchita Rábago de la Fundación Jiménez Díaz,
Madrid (Spain). JG-R is supported by a predoctoral grant from the
Fundacion Investigacion Biomedica Puerta de Hierro. Salary support to
SG is provided by ISCIII-FEDER (CP11/00018). MS-B is supported
by a Miguel Servet contract from ISCIII-FEDER (CP11/00018). The
Instituto de Investigación Marqués de Valdecilla (IDIVAL) is partly
funded by the Sociedad para el Desarrollo Regional de Cantabria
(SODERCAN)
An integrative genomic and transcriptomic analysis reveals molecular pathways and networks regulated by copy number aberrations in basal-like, HER2 and luminal cancers
The inducible T-cell co-stimulator molecule is expressed on subsets of T cells and is a new marker of lymphomas of T follicular helper cell-derivation
International audienceBACKGROUND: T follicular helper (T(FH)) cells reside in the light zone of germinal centers and are considered the cell of origin of angioimmunoblastic T-cell lymphoma. Recently, CXCL13, PD-1 and SAP were described as useful markers for T(FH) cells and angioimmunoblastic T-cell lymphoma but also reported in some peripheral T-cell lymphomas, not otherwise specified. DESIGN AND METHODS: In the present study the expression pattern of ICOS protein was investigated by immunohistochemistry-based techniques in routine sections of normal lymphoid tissues and 633 human lymphomas. RESULTS: Cells strongly positive for ICOS were restricted to the light zone of germinal centers and co-expressed T(FH)-associated molecules. In addition, weak to moderate ICOS expression was observed in a small proportion of FOXP3-positive cells. In lymphomas, ICOS expression was confined to angioimmunoblastic T-cell lymphoma (85/86), peripheral T-cell lymphomas of follicular variant (18/18) and a proportion of peripheral T-cell lymphomas, not otherwise specified (24/56) that also expressed other T(FH)-associated molecules. CONCLUSIONS: ICOS is a useful molecule for identifying T(FH) cells and its restricted expression to angioimmunoblastic T-cell lymphoma and a proportion of peripheral T-cell lymphomas, not otherwise specified (showing a T(FH)-like profile) suggests its inclusion in the antibody panel for diagnosing T(FH)-derived lymphomas. Our findings provide further evidence that the histological spectrum of T(FH)-derived lymphomas is broader than previously assumed
PLCG1 mutations in cutaneous T-cell lymphomas
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of primary
cutaneous T-cell lymphoproliferative processes, mainly composed of
mycosis fungoides and Sezary syndrome, the aggressive forms of which
lack an effective treatment. The molecular pathogenesis of CTCL is
largely unknown, although neoplastic cells show increased signaling from
T-cell receptors (TCRs). DNAs from 11 patients with CTCL, both normal
and tumoral, were target-enriched and sequenced by massive parallel
sequencing for a selection of 524 TCR-signaling-related genes.
Identified variants were validated by capillary sequencing. Multiple
mutations were found that affected several signaling pathways, such as
TCRs, nuclear factor kappa B, or Janus kinase/signal transducer and
activator of transcription, but PLCG1 was found to be mutated in 3
samples, 2 of which featured a redundant mutation (c.1034T>C, S345F) in
exon 11 that affects the PLCx protein catalytic domain. This mutation
was further analyzed by quantitative polymerase chain reaction
genotyping in a new cohort of 42 patients with CTCL, where it was found
in 19% of samples. Immunohistochemical analysis for nuclear factor of
activated T cells (NFAT) showed that PLCG1-mutated cases exhibited
strong NFAT nuclear immunostaining. Functional studies demonstrated that
PLCG1 mutants elicited increased downstream signaling toward NFAT
activation, and inhibition of this pathway resulted in reduced CTCL cell
proliferation and cell viability. Thus, increased proliferative and
survival mechanisms in CTCL may partially depend on the acquisition of
somatic mutations in PLCG1 and other genes that are essential for normal
T-cell differentiation