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RARS  -  arginyl-tRNA synthetase

Homo sapiens

Synonyms: ArgRS, Arginine--tRNA ligase, cytoplasmic, Arginyl-tRNA synthetase, DALRD1, HLD9
 
 
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Disease relevance of RARS

 

High impact information on RARS

 

Chemical compound and disease context of RARS

  • In the present study, we analyzed the expression of platelet glycoprotein (GP) Ia/IIa, IIb/IIIa, Ib/IX, and IV in 21 MDS patients (12 RA, 2 RARS, 4 RAEB, 1 RAEB-T, 2 CMML) and healthy controls by flowcytometric analysis and quantitation of platelet GP RNA using fluorescence-based PCR [10].
  • We report on a 21-year-old man with a mediastinal germ cell tumor (MGCT) who developed a myelodysplastic syndrome (MDS) (refractory anemia with ringed sideroblasts, RARS) 10 months after the start of successful treatment with cisplatin, etoposide, ifosfamide, and paclitaxel [4].
  • We examined the efficacy of thalidomide in 34 patients with myelodysplastic syndromes (MDS): five RAEB-T, four RAEB, three CMML, six RARS, and 16 RA [11].
  • ATG, cyclosporine, and methylprednisone induced complete (N=4) or partial (N=1) remission in five patients (16% of total; RA, two patients; RARS, two patients; and RAEB, one patient) [12].
  • DESIGN AND METHODS: In a pilot phase II study we treated 26 patients with low risk MDS (13 RA, 2 RARS, 2 CMML, 9 RAEB with blasts < 10%) with amifostine (200 mg/m(2 )x 3/week for 4 weeks) [13].
 

Biological context of RARS

  • Caspase inhibition reduced apoptosis, increased proliferation and enhanced erythroid colony growth from CD34+ cells in RARS, but showed no effect on normal cells [14].
  • This may suggest that the increased platelet counts observed in RARS may be caused by increased S-TPO levels [3].
  • In vitro erythropoiesis was decreased in most of the patients, with significantly lower number of BFU-E in "advanced" MDS than in RA/RARS patients [15].
  • RESULTS: In untreated RARS, the proportion of hypochromic erythrocytes (Hypo-e, median 6.2%, range 1.1-8%) and hypochromic reticulocytes (Hypo-r, median 45%, range 22-48%), as well as mean corpuscular volume (MCV, median 101 fL) were significantly elevated compared to corresponding values in controls [16].
  • DNA sequence analysis identified an open reading frame of 1983 nucleotides with 87% homology to other mammalian ArgRS genes [17].
 

Anatomical context of RARS

  • Burst-forming units erythroid (BFU-E, 75 +/- 88/10(4) CD34+ cells, X +/- s.d.) and colony-forming units E (CFU-E) were observed in eight of the 13 cases (62%) with refractory anemia with or without ring sideroblasts (RA and RARS) and one of the five cases with RA with excess of blasts or in transformation (RAEB and RAEB-T) [18].
  • FACS and morphology analysis after 7 days of suspension culture demonstrated partial differentiation along the erythroid lineage in cases with RA/RARS (75%) and RAEB/RAEB-T (66%) reflected by the presence of erythroblasts and normoblasts with variable expression of CD34, CD36 and Glycophorin A [18].
  • We studied bone marrow from 10 RARS patients, two of whom were also investigated after successful treatment [14].
  • Treatment with granulocyte colony-stimulating factor plus erythropoietin may improve haemoglobin levels in patients with ringsideroblastic anaemia (RARS) and reduce bone marrow apoptosis [14].
  • Patients with a low risk of developing acute leukaemia were included, i.e. refractory anaemia (RA), RA with ringed sideroblasts (RARS) and RA with excess blasts (RAEB), providing the percentage of myeloblasts in the bone marrow did not exceed 10% [19].
 

Associations of RARS with chemical compounds

  • Like arginyl-tRNA synthetases from other organisms, human placental arginyl-tRNA synthetase catalyzes the arginine-dependent ATP-PPi exchange reaction only in the presence of tRNA [20].
  • Thus, serum tryptase concentrations were higher in RA (16.6 +/- 14.3 ng/ml), RARS (12.9 +/- 8.2), and CMML (16.5 +/- 7.6) compared to RAEB/-t (8.7 +/- 3.8) [21].
  • Crucial role of the high-loop lysine for the catalytic activity of arginyl-tRNA synthetase [22].
  • A single nucleotide change, resulting in a Cys to Tyr substitution at position 599 of arginyl-tRNA synthetase, is responsible for the defective phenotype of the thermosensitive and arginine hyper-auxotroph Arg-1 cell line [23].
  • The three regions that are crucial for activation of ArgRS are the terminal adenosine, the D-loop, and the anticodon stem-loop of tRNA [24].
 

Physical interactions of RARS

 

Other interactions of RARS

  • The C-terminal appended domain of human cytosolic leucyl-tRNA synthetase is indispensable in its interaction with arginyl-tRNA synthetase in the multi-tRNA synthetase complex [27].
  • PGP positivity was rare in 'low risk' MDS (RA and RARS: 2/12 cases) as opposed to 'high risk' MDS (RAEB, RAEB-T, CMML: 25/60 cases) and MDS-AML (7/10 cases) (p = 0.04) [28].
  • Moreover, their expression inversely correlates with tumor diameter and with RARS expression (P < 0.05), but directly correlates with p43 secretion (P < 0.02) [29].
  • Increased levels of platelet GPIb and GPIIb RNA were significantly more prominent among patients with RAEB(-T)/CMML (p<0. 05) in comparison to patients with RA/RARS [10].
  • The above data suggest that the combination of rhEpo and GM-CSF should be recommended in all cases with RARS [30].
 

Analytical, diagnostic and therapeutic context of RARS

  • Fas ligation increased apoptosis and decreased colony growth equally in RARS and controls, but caused significantly more caspase activation in RARS (P < 0.01) [14].
  • Using ELISA technology we measured endogenous serum levels in 93 patients with MDS: 29 RA, 1 RARS, 31 RAEB, 23 RAEBt, 9 CMML [31].
  • Refractory cytopenia with multilineage dysplasia and RAEB II seemed to have different prognoses from RA or RARS and RAEB I, respectively [32].
  • TUNEL labeling of bone marrow from 24 patients with MDS revealed significant positivity in 10 of 11 patients with refractory anemia (RA), five of seven with RA and excess of blasts (RAEB), all three patients with RAEB in transformation (RAEB-t), and all three patients with RA with ring sideroblasts (RARS) [33].
  • The Chronic Leukemia Working Party of the EBMT has collected data on 118 patients of median age 24 years (range 0.3 to 53 years) who underwent an allogeneic bone marrow transplantation from unrelated donors for treatment of MDS or secondary AML (RA/RARS, n = 24; RAEB, n = 26; RAEB-t, n = 34; CMML, n = 12; sAML, n = 22) between 1986 and 1996 [34].

References

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  2. Growth analysis of marrow CD34-positive hematopoietic progenitor cells in patients with myelodysplastic syndromes. Asano, H., Hotta, T., Ichihara, M., Murate, T., Kobayashi, M., Saito, H. Leukemia (1994) [Pubmed]
  3. Spontaneous and cytokine-induced thrombocytopenia in myelodysplastic syndromes: serum thrombopoietin levels and bone marrow morphology. Scandinavian MDS Group, Sweden and Norway. Hellström-Lindberg, E., Kanter-Lewensohn, L., Nichol, J., Ost, A. Br. J. Haematol. (1999) [Pubmed]
  4. Myelodysplastic syndrome (RARS) with +i(12p) abnormality in a patient 10 months after diagnosis and successful treatment of a mediastinal germ cell tumor (MGCT). Christodoulou, J., Schoch, C., Schnittger, S., Haferlach, T. Ann. Hematol. (2004) [Pubmed]
  5. c-mpl expression in hematologic disorders. Bouscary, D., Prudhomme, C., Quesnel, B., Melle, J., Picard, F., Dreyfus, F. Leuk. Lymphoma (1995) [Pubmed]
  6. A novel means for dealing with L-canavanine, a toxic metabolite. Rosenthal, G.A., Dahlman, D.L., Janzen, D.H. Science (1976) [Pubmed]
  7. Recent emergence of the modern genetic code: a proposal. Syvanen, M. Trends Genet. (2002) [Pubmed]
  8. Bmi-1 is useful as a novel molecular marker for predicting progression of myelodysplastic syndrome and patient prognosis. Mihara, K., Chowdhury, M., Nakaju, N., Hidani, S., Ihara, A., Hyodo, H., Yasunaga, S., Takihara, Y., Kimura, A. Blood (2006) [Pubmed]
  9. Aberrant mitochondrial iron distribution and maturation arrest characterize early erythroid precursors in low-risk myelodysplastic syndromes. Tehranchi, R., Invernizzi, R., Grandien, A., Zhivotovsky, B., Fadeel, B., Forsblom, A.M., Travaglino, E., Samuelsson, J., Hast, R., Nilsson, L., Cazzola, M., Wibom, R., Hellström-Lindberg, E. Blood (2005) [Pubmed]
  10. Platelet glycoprotein expression in patients with myelodysplastic syndrome. Seidl, C., Siehl, J., Ganser, A., Hofmann, W.K., Fischer, M., Kirchmaier, C.M., Hoelzer, D., Seifried, E. Thromb. Res. (2000) [Pubmed]
  11. Thalidomide for the treatment of patients with myelodysplastic syndromes. Strupp, C., Germing, U., Aivado, M., Misgeld, E., Haas, R., Gattermann, N. Leukemia (2002) [Pubmed]
  12. Antithymocyte globulin (ATG)-based therapy in patients with myelodysplastic syndromes. Yazji, S., Giles, F.J., Tsimberidou, A.M., Estey, E.H., Kantarjian, H.M., O'Brien, S.A., Kurzrock, R. Leukemia (2003) [Pubmed]
  13. Amifostine in the treatment of low-risk myelodysplastic syndromes. Grossi, A., Fabbri, A., Santini, V., Leoni, F., Nozzoli, C., Longo, G., Pagliai, G., Ciolli, S., Rossi Ferrini, P. Haematologica (2000) [Pubmed]
  14. Apoptosis in refractory anaemia with ringed sideroblasts is initiated at the stem cell level and associated with increased activation of caspases. Hellström-Lindberg, E., Schmidt-Mende, J., Forsblom, A.M., Christensson, B., Fadeel, B., Zhivotovsky, B. Br. J. Haematol. (2001) [Pubmed]
  15. Biological and clinical significance of clonogenic assays in patients with myelodysplastic syndromes. Marisavljević, D., Rolović, Z., Sefer, D., Basara, N., Ilić, D., Bosković, D., Colović, M. Med. Oncol. (2002) [Pubmed]
  16. Hypochromic red blood cells in low-risk myelodysplastic syndromes: effects of treatment with hemopoietic growth factors. Ljung, T., Bäck, R., Hellström-Lindberg, E. Haematologica (2004) [Pubmed]
  17. Cloning and characterization of cDNA encoding a human arginyl-tRNA synthetase. Girjes, A.A., Hobson, K., Chen, P., Lavin, M.F. Gene (1995) [Pubmed]
  18. CD34+/CD36- cells from myelodysplasia patients have a limited capacity to proliferate but can differentiate in response to Epo and MGF stimulation. Brada, S.J., de Wolf, J.T., Hendriks, D.W., Smit, J.W., Vellenga, E. Leukemia (1998) [Pubmed]
  19. Effect of subcutaneously administered human recombinant erythropoietin on erythropoiesis in patients with myelodysplasia. van Kamp, H., Prinsze-Postema, T.C., Kluin, P.M., den Ottolander, G.J., Beverstock, G.C., Willemze, R., Fibbe, W.E. Br. J. Haematol. (1991) [Pubmed]
  20. Kinetic mechanism of arginyl-tRNA synthetase from human placenta. Wang, H.Y., Pan, F. Int. J. Biochem. (1984) [Pubmed]
  21. Serum tryptase measurements in patients with myelodysplastic syndromes. Sperr, W.R., Stehberger, B., Wimazal, F., Baghestanian, M., Schwartz, L.B., Kundi, M., Semper, H., Jordan, J.H., Chott, A., Drach, J., Jäger, U., Geissler, K., Greschniok, A., Horny, H.P., Lechner, K., Valent, P. Leuk. Lymphoma (2002) [Pubmed]
  22. Crucial role of the high-loop lysine for the catalytic activity of arginyl-tRNA synthetase. Sekine , S., Shimada, A., Nureki, O., Cavarelli, J., Moras, D., Vassylyev, D.G., Yokoyama, S. J. Biol. Chem. (2001) [Pubmed]
  23. The tRNA-dependent activation of arginine by arginyl-tRNA synthetase requires inter-domain communication. Lazard, M., Agou, F., Kerjan, P., Mirande, M. J. Mol. Biol. (2000) [Pubmed]
  24. Determinants in tRNA for activation of arginyl-tRNA synthetase: evidence that tRNA flexibility is required for the induced-fit mechanism. Guigou, L., Mirande, M. Biochemistry (2005) [Pubmed]
  25. Precursor of pro-apoptotic cytokine modulates aminoacylation activity of tRNA synthetase. Park, S.G., Jung, K.H., Lee, J.S., Jo, Y.J., Motegi, H., Kim, S., Shiba, K. J. Biol. Chem. (1999) [Pubmed]
  26. A multifunctional repeated motif is present in human bifunctional tRNA synthetase. Rho, S.B., Lee, J.S., Jeong, E.J., Kim, K.S., Kim, Y.G., Kim, S. J. Biol. Chem. (1998) [Pubmed]
  27. The C-terminal appended domain of human cytosolic leucyl-tRNA synthetase is indispensable in its interaction with arginyl-tRNA synthetase in the multi-tRNA synthetase complex. Ling, C., Yao, Y.N., Zheng, Y.G., Wei, H., Wang, L., Wu, X.F., Wang, E.D. J. Biol. Chem. (2005) [Pubmed]
  28. Expression of the multidrug resistance P-glycoprotein and its relationship to hematological characteristics and response to treatment in myelodysplastic syndromes. Lepelley, P., Soenen, V., Preudhomme, C., Lai, J.L., Cosson, A., Fenaux, P. Leukemia (1994) [Pubmed]
  29. miR-15a and miR-16-1 down-regulation in pituitary adenomas. Bottoni, A., Piccin, D., Tagliati, F., Luchin, A., Zatelli, M.C., degli Uberti, E.C. J. Cell. Physiol. (2005) [Pubmed]
  30. Treatment of anemia in low risk myelodysplastic syndromes with granulocyte-macrophage colony-stimulating factor plus recombinant human erythropoietin. Economopoulos, T., Mellou, S., Papageorgiou, E., Pappa, V., Kokkinou, V., Stathopoulou, E., Pappa, M., Raptis, S. Leukemia (1999) [Pubmed]
  31. Endogenous FLT-3 ligand serum levels are associated with disease stage in patients with myelodysplastic syndromes. Zwierzina, H., Anderson, J.E., Rollinger-Holzinger, I., Torok-Storb, B., Nuessler, V., Lyman, S.D. Leukemia (1999) [Pubmed]
  32. Application of different prognostic scoring systems and comparison of the FAB and WHO classifications in Korean patients with myelodysplastic syndrome. Lee, J.H., Lee, J.H., Shin, Y.R., Lee, J.S., Kim, W.K., Chi, H.S., Park, C.J., Seo, E.J., Lee, K.H. Leukemia (2003) [Pubmed]
  33. Spontaneous intramedullary apoptosis is present in disorders other than myelodysplasia. Irvine, A.E., Magill, M.K., Somerville, L.E., McMullin, M.F. Exp. Hematol. (1998) [Pubmed]
  34. Unrelated bone marrow transplantation in patients with myelodysplastic syndromes and secondary acute myeloid leukemia: an EBMT survey. European Blood and Marrow Transplantation Group. Arnold, R., de Witte, T., van Biezen, A., Hermans, J., Jacobsen, N., Runde, V., Gratwohl, A., Apperley, J.F. Bone Marrow Transplant. (1998) [Pubmed]
 
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