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The genome of Rickettsia prowazekii, the causative agent of typhus
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Notes levels: 2 1O-2, 10-3, and 10-4. The distinct MRD levels appeared to have independent prognostic value (P [trend] < 0.001) at all time points. Therefore, monitoring of childhood ALL patients at multiple time points gave clinically relevant insights into the effectiveness of treatment. More importantly, by using the kinetics of tumor reduction during the first three months of therapy, it was possible to recognize a low risk group (- 43% of patients) with a three year relapse rate of only 2%, an intermediate risk group (- 43%) with a three year relapse rate of - 2.5%, and a high risk group (- 15%) with a three year relapse rate of 75%. By subsequent MRD monitoring it is possible to distinguish within the prognosis: patients with MRD in their bone marrow at one year after diagnosis have a relapse rate of 67%, which is significantly worse than the low relapse rate (10%) of patients with MRD-PCR negativity at that time point. The technical and clinical data of our collaborative study show that multicentre MRD studies are feasible and that a clinically relevant MRD-based risk group classification can be achieved. This information can now be used for the design of new childhood ALL protocols with PRD-based stratification of treatment. J.J.M. van Dongen (5) Erasmus University Rotterdam Rotterdam, the Netherlands
(5)Lancet 1998 ; 352 : 1731-8 The genome of Rick&Ma prowazekii, the causative agent of typhus Rickettsiaprowazekii is the causative agent of epidemic typhus. Clinical manifestations of the disease include chills, fever, malaise, pain, headache, nausea, and vomiting. Typhus, which is transmitted by the body louse Pediculus humunus,killed several million people in armies, ghettos, and prison camps during the First and Second World Wars. It still prevails today, especially in eastern parts of the world.
The sequence of the 1.1 Mb genome of R. prowazekiihas recently been determined. This genome contains only 834 protein coding genes, and as much as 24% of the genome appears to be non-coding DNA. Many genes involved in the biosynthesis of amino acids and nucleosides are missing. These genes seem to have been deleted and replaced by homologues in the eukaryotic host genome. Indeed, gene elimination appears to be an on-going process in Rickettsia.For example, the metKgene which codes for S-adenosylmethionine synthetase has been inactivated in several Rickettsiaspecies independently of one another. It has been speculated that the high fraction of non-coding DNA may correspond to old genes which have been destroyed beyond recognition, but not yet completely eliminated form the genome. R. prowazekii is equipped with an ATP/ADP transport system for the import of cytoplasmic ATP in exchange for ADP during the early phase of the infectious cycle. The genome also contains a complete set of genes coding components of the respiratory chain complexes, which are used to produce ATP during the latter phase of the infectious cycle when R. prowazekiihas depleted the host cell cytoplasm of ATP. Phylogenetic analyses suggest that the energy production system in mitochondria may have been derived from an ancestor of the Rickettsia.Functional analyses have so far been hampered by the fact that Rickettsiu are obligate intracellular parasites for which there is a lack of genetic tools to study mutants. With the help of the genome sequence an ordered clone bank covering the entire R. prowazekiigenome has been constructed. This ordered clone bank can serve as a resource for systematic analysis of the R.prowuzekiimetabolism and assist in detailed studies of the virulence factors involved in the disease. S. Anderson (6) Uppsala University 75 1 24 Uppsala, Sweden (6) Nature 1998 ; 396 : 113-40
Notes levels: 2 1O-2, 10-3, and 10-4. The distinct MRD levels appeared to have independent prognostic value (P [trend] < 0.001) at all time points. Therefore, monitoring of childhood ALL patients at multiple time points gave clinically relevant insights into the effectiveness of treatment. More importantly, by using the kinetics of tumor reduction during the first three months of therapy, it was possible to recognize a low risk group (- 43% of patients) with a three year relapse rate of only 2%, an intermediate risk group (- 43%) with a three year relapse rate of - 2.5%, and a high risk group (- 15%) with a three year relapse rate of 75%. By subsequent MRD monitoring it is possible to distinguish within the prognosis: patients with MRD in their bone marrow at one year after diagnosis have a relapse rate of 67%, which is significantly worse than the low relapse rate (10%) of patients with MRD-PCR negativity at that time point. The technical and clinical data of our collaborative study show that multicentre MRD studies are feasible and that a clinically relevant MRD-based risk group classification can be achieved. This information can now be used for the design of new childhood ALL protocols with PRD-based stratification of treatment. J.J.M. van Dongen (5) Erasmus University Rotterdam Rotterdam, the Netherlands
(5)Lancet 1998 ; 352 : 1731-8 The genome of Rick&Ma prowazekii, the causative agent of typhus Rickettsiaprowazekii is the causative agent of epidemic typhus. Clinical manifestations of the disease include chills, fever, malaise, pain, headache, nausea, and vomiting. Typhus, which is transmitted by the body louse Pediculus humunus,killed several million people in armies, ghettos, and prison camps during the First and Second World Wars. It still prevails today, especially in eastern parts of the world.
The sequence of the 1.1 Mb genome of R. prowazekiihas recently been determined. This genome contains only 834 protein coding genes, and as much as 24% of the genome appears to be non-coding DNA. Many genes involved in the biosynthesis of amino acids and nucleosides are missing. These genes seem to have been deleted and replaced by homologues in the eukaryotic host genome. Indeed, gene elimination appears to be an on-going process in Rickettsia.For example, the metKgene which codes for S-adenosylmethionine synthetase has been inactivated in several Rickettsiaspecies independently of one another. It has been speculated that the high fraction of non-coding DNA may correspond to old genes which have been destroyed beyond recognition, but not yet completely eliminated form the genome. R. prowazekii is equipped with an ATP/ADP transport system for the import of cytoplasmic ATP in exchange for ADP during the early phase of the infectious cycle. The genome also contains a complete set of genes coding components of the respiratory chain complexes, which are used to produce ATP during the latter phase of the infectious cycle when R. prowazekiihas depleted the host cell cytoplasm of ATP. Phylogenetic analyses suggest that the energy production system in mitochondria may have been derived from an ancestor of the Rickettsia.Functional analyses have so far been hampered by the fact that Rickettsiu are obligate intracellular parasites for which there is a lack of genetic tools to study mutants. With the help of the genome sequence an ordered clone bank covering the entire R. prowazekiigenome has been constructed. This ordered clone bank can serve as a resource for systematic analysis of the R.prowuzekiimetabolism and assist in detailed studies of the virulence factors involved in the disease. S. Anderson (6) Uppsala University 75 1 24 Uppsala, Sweden (6) Nature 1998 ; 396 : 113-40