+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets

, : Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets. Blood 119(24): 5795-5806

The pathogenesis of hepatosplenic T-cell lymphoma (HSTL), a rare entity mostly derived from T cells and usually with a fatal outcome, remains largely unknown. In this study, HSTL samples (7 and 2αβ) and the DERL2 HSTL cell line were subjected to combined gene-expression profiling and array-based comparative genomic hybridization. Compared with other T-cell lymphomas, HSTL had a distinct molecular signature irrespective of TCR cell lineage. Compared with peripheral T-cell lymphoma, not otherwise specified and normal T cells, HSTL overexpressed genes encoding NK-cell–associated molecules, oncogenes (FOS and VAV3), the sphingosine-1-phosphatase receptor 5 involved in cell trafficking, and the tyrosine kinase SYK, whereas the tumor-suppressor gene AIM1 (absent in melanoma 1) was among the most down-expressed. We found highly methylated CpG islands of AIM1 in DERL2 cells, and decitabine treatment induced a significant increase in AIM1 transcripts. Syk was present in HSTL cells and DERL2 cells contained phosphorylated Syk and were sensitive to a Syk inhibitor in vitro. Genomic profiles confirmed recurrent isochromosome 7q (n = 6/9) without alterations at the SYK and AIM1 loci. Our results identify a distinct molecular signature for HSTL and highlight oncogenic pathways that offer rationale for exploring new therapeutic options such as Syk inhibitors and demethylating agents.


PMID: 22510872

DOI: 10.1182/blood-2011-12-396150

Other references

KinghornEditor-in-Chief, 1999: Changes for volume 62. Journal of Natural Products 62(1): 1-1

Palladino M.A.Jr; Figari I.S.; Fendly B.; Bald L.; Rice G.C.; Deleo A.B., 1990: In vivo antitumor activity of rtnf alpha against meth a sarcoma requires l3t4 positive and lty 2 positive t cells possible role of tgf beta and augmentation of class i mhc expression. FASEB Journal 4(7): A1867

Farcet, M.R.; Planitzer, C.B.; Stein, O.; Modrof, J.; Kreil, T.R., 2010: Hepatitis A virus antibodies in immunoglobulin preparations. Persons with primary immune deficiency receive intravenous immunoglobulin (IVIG) as antibody replacement therapy. These patients depend on the presence of protective antibody levels against circulating pathogens in IVIG. The incidence of hepatitis...

Nikiforoff, C.C.; Humbert, R.P.; Cady, J.G., 1948: The hardpan in certain soils of the Coastal Plain. The hardpans of the Leonardtown series are compacted and uncemented, and represent a type of formation fundamentally different from the chemically cemented hardpans. Laboratory and electron-microscope "investigations suggest that the hardpan...

Heredia-Pi, I.B.; Servan-Mori, E.; Reynales-Shigematsu, L.Myriam.; Bautista-Arredondo, S., 2012: The maximum willingness to pay for smoking cessation method among adult smokers in Mexico. To estimate the maximum willingness to pay (WTP) for an effective smoking cessation treatment among smokers in Mexico and to identify the environmental, demographic, and socioeconomic factors associated with the WTP. A cross-sectional study was co...

Mayer, M.L., 1985: A calcium-activated chloride current generates the after-depolarization of rat sensory neurones in culture. Neurones from the dorsal root ganglia of 1-day-old rat pups were grown in dissociated culture and voltage clamped using patch electrodes for whole-cell recording. The pipettes were filled with either 140 mM-KCl or CsCl. Depolarizing voltage jumps...

Jung A.; Mermillod B.; Barras C.; Baud M.; Courvoisier B., 1981: Inhibition by 2 di phosphonates of bone lysis in tumor conditioned media. Neonatal mouse calvaria were cultured in sterile conditions in different media. Osteolysis was estimated by the amount of 45Ca released from bone to medium, the mice being given injections of 45Ca on their day of birth. An increase bone lysis is o...

Zonn, S.V., 1963: Principles of classifying forest soils & methods of studying them.. Forest soils are divided into series of types according to the way in which chemical elements enter the soil & migrate within it, into groups of types according to accumulation of organic matter, & into types according to the cycle of elements in...

Schreiner, H.C.; Dunner, D.L.; Meltzer, H.L.; Fieve, R.R., 1979: The relationship of the lithium erythrocyte: plasma ratio to plasma lithium level. The relationship of the lithium erythrocyte:plasma ratio to plasma lithium concentration was reviewed in inpatients and outpatients with affective disorders. For some patients, there was a linear correlation between the erythrocyte lithium:plasma...

Chardot C.; Adolff O.Reilly A., 1968: Present sequelae and psychological repercussions after halsteds operation a detailed investigation into the cases of 95 patients. Presse Medicale 76(38): 1813-1816