245 research outputs found
t(X;14)(p11.4;q32.33) IGH/GPR34
Short communication on t(X;14)(p11.4;q32.33) IGH/GPR34, with data on clinics, and the genes implicated
FOXP1 (forkhead box P1)
Review on FOXP1 (forkhead box P1), with data on DNA, on the protein encoded, and where the gene is implicated
Genetics of Chronic Lymphocytic Leukemia: Practical Aspects and Prognostic Significance
status: publishe
Non-radioactive in situ hybridization for the detection and monitoring of trisomy 12 in B-cell chronic lymphocytic leukaemia
Evidence for position effects as a variant ETV6-mediated leukemogenic mechanism in myeloid leukemias with a t(4;12)(q11-q12;p13) or t(5;12)(q31;p13)
The ETV6 gene (first identified as TEL) is a frequent target of chromosomal translocations in both myeloid and lymphoid leukemias. At present, more than 40 distinct translocations have been cytogenetically described, of which 13 have now also been characterized at the molecular level. These studies revealed the generation of in-frame fusion genes between different domains of ETV6 and partner genes encoding either kinases or transcription factors. However, in a number of cases-including a t(6;12)(q23;p13), the recurrent t(5;12)(q31;p13), and some cases of the t(4;12)(q11-q12;p13) described in this work-functionally significant fusions could not be identified, raising the question as to what leukemogenic mechanism is implicated in these cases. To investigate this, we have evaluated the genomic regions at 4q11-q12 and 5q31, telomeric to the breakpoints of the t(4;12)(q11-q12;p13) and t(5;12)(q31;p13). The homeobox gene GSH2 at 4q11-q12 and the IL-3/CSF2 locus at 5q31 were found to be located close to the respective breakpoints. In addition, GSH2 and IL-3 were found to be ectopically expressed in the leukemic cells, suggesting that expression of GSH2 and IL-3 was deregulated by the translocation. Our results indicate that, besides the generation of fusion transcripts, deregulation of the expression of oncogenes could be a variant leukemogenic mechanism for translocations involving the 5' end of ETV6, especially for those translocations lacking functionally significant fusion transcripts
RPL5 on 1p22.1 is recurrently deleted in multiple myeloma and its expression is linked to bortezomib response
Chromosomal region 1p22 is deleted in 6520% of multiple myeloma (MM) patients, suggesting the presence of an unidentified tumor suppressor. Using high-resolution genomic profiling, we delimit a 58 kb minimal deleted region (MDR) on 1p22.1 encompassing two genes: ectopic viral integration site 5 (EVI5) and ribosomal protein L5 (RPL5). Low mRNA expression of EVI5 and RPL5 was associated with worse survival in diagnostic cases. Patients with 1p22 deletion had lower mRNA expression of EVI5 and RPL5, however, 1p22 deletion status is a bad predictor of RPL5 expression in some cases, suggesting that other mechanisms downregulate RPL5 expression. Interestingly, RPL5 but not EVI5 mRNA levels were
significantly lower in relapsed patients responding to bortezomib and; both in newly diagnosed and relapsed patients, bortezomib treatment could overcome their bad prognosis by raising their progression-free survival to equal that of patients with high RPL5 expression.
In conclusion, our genetic data restrict the MDR on 1p22 to EVI5 and RPL5 and although the role of these genes in promoting MM progression remains to be determined, we identify RPL5 mRNA expression as a biomarker for initial response to bortezomib in relapsed patients and subsequent survival benefit after long-term treatment in newly diagnosed and relapsed patients
Fusion of EML1 to ABL1 in T-cell acute lymphoblastic leukemia with cryptic t(9;14)(q34;q32)
The BCR-ABL1 fusion kinase is frequently associated with chronic myeloid leukemia and B-cell acute lymphoblastic leukemia but is rare in T-cell acute lymphoblastic leukemia (T-ALL). We recently identified NUP214-ABL1 as a variant ABL1 fusion gene in 6% of T-ALL patients. Here we describe the identification of another ABL1 fusion, EML1-ABL1, in a T-ALL patient with a cryptic t(9;14)(q34;q32) associated with deletion of CDKN2A (p16) and expression of TLX1 (HOX11). Echinoderm microtubule-associated protein-like 1-Abelson 1 (EML1-ABL1) is a constitutively phosphorylated tyrosine kinase that transforms Ba/F3 cells to growth factor-independent growth through activation of survival and proliferation pathways, including extracellular signal-related kinase 1/2 (Erk1/2), signal transducers and activators of transcription 5 (Stat5), and Lyn kinase. Deletion of the coiled-coil domain of EML1 abrogated the transforming properties of the fusion kinase. EML1-ABL1 and breakpoint cluster region (BCR)-ABL1 were equally sensitive to the tyrosine kinase inhibitor imatinib. These data further demonstrate the involvement of ABL1 fusions in the pathogenesis of T-ALL and identify EML1-ABL1 as a novel therapeutic target of imatinib
HAUSGARTEN: Multidisciplinary investigations at a deep-sea, long-term observatory in the Arctic Ocean
The marine Arctic has played an essential role in the history of our planet over the past 130 million years and contributes considerably to the present functioning of Earth and its life. The global cycles of a variety of materials fundamental to atmospheric conditions and thus to life depend to a signifi cant extent on Arctic marine processes (Aargaard et al., 1999). The past decades have seen remarkable changes in key Arctic variables. The decrease of sea-ice extent and sea-ice thickness in the past decade is statistically signifi - cant (Cavalieri et al., 1997; Parkinson et al., 1999; Walsh and Chapman, 2001; Partington et al., 2003; Johannessen et al., 2004). There have also been large changes in the upper and intermediate layers of the ocean, which have environmental implications. For instance, the deep Greenland Sea has continued its decadal trend towards warmer and saltier conditions, with a corresponding decrease in oxygen content, refl ecting the lack of effective local convection and ventilation (Dickson et al., 1996; Boenisch et al., 1997). Changes in temperature and salinity and associated shifts in nutrient distributions will directly affect the marine biota on multiple scales from communities and populations to individuals, consequently altering food-web structures and ecosystem functioning (Benson and Trites, 2002; Moore, 2003; Schumacher et al., 2003; Wiltshire and Manly, 2004; Perry et al., 2005). Today, we do not know whether the severe alterations in abiotic parameters represent perturbations due to human impacts, natural long-term trends, or new equilibriums (Bengtson et al., 2004). Because Arctic organisms are highly adapted to extreme environmental conditions with strong seasonal forcing, the accelerating rate of recent climate change challenges the resilience of Arctic life (Hassol, 2004). The entire system is likely to be severely affected by changing ice and water conditions, varying primary production and food availability to faunal communities, an increase in contaminants, and possibly increased UV irradiance. The stability of a number of Arctic populations and ecosystems is probably not strong enough to withstand the sum of these factors, which might lead to a collapse of subsystems. To detect and track the impact of large-scale environmental changes in the transition zone between the northern North Atlantic and the central Arctic Ocean, and to determine experimentally the factors controlling deep-sea biodiversity, the German Alfred Wegener Institute for Polar and Marine Research (AWI) established the deepsea, long-term observatory HAUSGARTEN, representing the fi rst, and by now only, open-ocean, long-term station in a polar region
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