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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Breitenbuecher, Frank, et al.
(författare)
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A novel molecular mechanism of primary resistance to FLT3-kinase inhibitors in AML
- 2009
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 113:17, s. 4063-4073
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Tidskriftsartikel (refereegranskat)abstract
- Currently, FLT3 tyrosine kinase inhibitors (TKIs) are emerging as the most promising drug therapy to overcome the dismal prognosis of acute myelogenous leukemia (AML) patients harboring internal tandem duplications (ITDs) of FLT3. However, up-front drug resistance occurs in approximately 30% of patients, and molecular mechanisms of resistance are poorly understood. Here, we have uncovered a novel mechanism of primary resistance to FLT3 TKIs in AML: an FLT3 receptor harboring a nonjuxtamembrane ITD atypically integrating into the beta-2 sheet of the first kinase domain (FLT3_ITD627E) induces dramatic up-regulation of the anti-apoptotic myeloid cell leukemia 1 protein (MCL-1). Using RNA interference technology, deregulated MCL-1 protein expression was shown to play a major role in conferring the resistance phenotype of 32D_ITD627E cells. Enhanced and sustained binding of the adaptor protein GRB-2 to the FLT3_ITD627E receptor is involved in MCL-1 up-regulation and is independent from TKI (PKC412)-induced inhibition of the receptor kinase. Thus, we describe a new mechanism of primary resistance to TKIs, which operates by reprogramming local and distant signal transduction events of the FLT3 tyrosine kinase. The data presented suggest that particular ITDs of FLT3 may be associated with rewired signaling and differential responsiveness to TKIs. (Blood. 2009; 113: 4063-4073)
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| 3. |
- Huber, Birgit, et al.
(författare)
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Ochrobactrum pituitosum sp. nov., isolated from an industrial environment.
- 2010
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Ingår i: International journal of systematic and evolutionary microbiology. - : Microbiology Society. - 1466-5026 .- 1466-5034. ; 60:Pt 2, s. 321-6
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Tidskriftsartikel (refereegranskat)abstract
- Strain CCUG 50899, a Gram-negative, rod-shaped, non-spore-forming, motile bacterium isolated from industrial environment in Sweden and tentatively assigned to the species Ochrobactrum anthropi, was studied in order to clarify its taxonomic status. 16S rRNA gene sequence similarities placed the strain in the genus Ochrobactrum, sharing highest similarity with the type strains of Ochrobactrum rhizosphaerae (99.3 %), Ochrobactrum thiophenivorans (98.7 %), Ochrobactrum pseudogrignonense (98.6 %) and Ochrobactrum grignonense (98.5 %). The fatty acid profile of [O. anthropi] CCUG 50899 (major fatty acids C(18 : 1)omega7c and C(19 : 0) cyclo omega8c and presence of C(18 : 1) 2-OH), the polar lipid profile (diphosphatidylglycerol, phosphatidylglycerol, phosphatidylmonomethylethanolamine, phosphatidylethanolamine, two unknown aminolipids and an unknown phospholipid), the presence of the quinone system ubiquinone Q-10 and a polyamine pattern with the major compounds putrescine and spermidine and moderate amounts of sym-homospermidine supported its affiliation to the genus Ochrobactrum. DNA-DNA reassociation experiments with the type strains of its closest relatives O. rhizosphaerae, O. pseudogrignonense, O. thiophenivorans and O. grignonense demonstrated that [O. anthropi] CCUG 50899 should be placed in a novel species, which is distinguishable from related species by a set of biochemical traits. Based on these data, reclassification of [O. anthropi] CCUG 50899 as the type strain of a novel species appears to be justified. Hence, we describe a novel species to accommodate this strain, for which we propose the name Ochrobactrum pituitosum sp. nov. The type strain is CCUG 50899(T) (=DSM 22207(T)).
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- Kämpfer, Peter, et al.
(författare)
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Deinococcus aquatilis sp. nov., isolated from water.
- 2008
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Ingår i: International journal of systematic and evolutionary microbiology. - : Microbiology Society. - 1466-5026 .- 1466-5034. ; 58:12, s. 2803-2806
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Tidskriftsartikel (refereegranskat)abstract
- A pale-pink strain (CCUG 53370(T)) from water was investigated by a polyphasic taxonomic approach. The cells stained Gram-positive and were rod-shaped and non-spore-forming. Analyses using the 16S rRNA gene sequence of the isolate showed that the organism belongs to the genus Deinococcus, with the highest sequence similarities to the type strains of Deinococcus ficus (94.4 %), Deinococcus navajonensis (94.3 %) and Deinococcus mumbaiensis (94.3 %). Chemotaxonomic data revealed that CCUG 53370(T) contains exclusively menaquinone MK-8 as the respiratory quinone and a complex polar lipid profile consisting of different unidentified glycolipids and polar lipids, two unknown phospholipids and three unknown phosphoglycolipids. As in other deinococci, one of these phosphoglycolipids was predominant in the profile, and it was identified in Deinococcus radiodurans as 2'-O-(1,2-diacyl-sn-glycero-3-phospho)-3'-O-(alpha-galactosyl)-N-D-glyceroyl alkylamine. Predominant fatty acids were C(16 : 1)omega7c, C(17 : 1)omega8c and C(17 : 1)omega9c. Biochemical and chemotaxonomic properties demonstrate that strain CCUG 53370(T) represents a novel species, for which the name Deinococcus aquatilis sp. nov. is proposed. The type strain is CCUG 53370(T) (=CCM 7524(T)).
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