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Characteristics of white blood cell count in acute lymphoblastic leukemia : A COST LEGEND phenotype-genotype study
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- Helenius, Marianne (författare)
- Tech Univ Denmark, Dept Hlth Technol, DK-2800 Copenhagen, Denmark.;Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark
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- Vaitkeviciene, Goda (författare)
- Vilnius Univ Hosp, Santaros Klin Ctr Pediat Oncol & Hematol, Vilnius, Lithuania.;Vilnius Univ, Vilnius, Lithuania
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- Abrahamsson, Jonas (författare)
- Sahlgrens Univ Hosp, Inst Clin Sci, Dept Paediat, Gothenburg, Sweden
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- Jonsson, Olafur Gisli (författare)
- Landspitali Univ Hosp, Dept Pediat, Reykjavik, Iceland
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- Lund, Bendik (författare)
- St Olavs Hosp, Dept Pediat, Trondheim, Norway
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- Harila-Saari, Arja H. (författare)
- Uppsala universitet,Institutionen för kvinnors och barns hälsa
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- Vettenranta, Kim (författare)
- Univ Helsinki, Helsinki, Finland.;Univ Helsinki, Childrens Hosp, Helsinki, Finland
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- Mikkel, Sirje (författare)
- Univ Tartu, Dept Hematol & Oncol, Tartu, Estonia
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- Stanulla, Martin (författare)
- Hannover Med Sch, Dept Pediat Hematol & Oncol, Hannover, Germany
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- Lopez-Lopez, Elixabet (författare)
- Univ Basque Country UPV EHU, Fac Sci & Technol, Dept Genet Phys Anthropol & Anim Physiol, Leioa, Spain.;BioCruces Bizkaia Hlth Res Inst, Pediat Oncol Grp, Baracaldo, Spain
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- Waanders, Esme (författare)
- Univ Med Ctr Utrecht, Dept Genet, Utrecht, Netherlands.;Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands
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- Madsen, Hans O. (författare)
- Univ Hosp, Rigshosp, Dept Clin Immunol, Copenhagen, Denmark
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- Marquart, Hanne Vibeke (författare)
- Univ Hosp, Rigshosp, Dept Clin Immunol, Copenhagen, Denmark
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- Modvig, Signe (författare)
- Univ Hosp, Rigshosp, Dept Clin Immunol, Copenhagen, Denmark
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- Gupta, Ramneek (författare)
- Tech Univ Denmark, Dept Hlth Technol, DK-2800 Copenhagen, Denmark.;Novo Nordisk Res Ctr Oxford, Oxford, England
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- Schmiegelow, Kjeld (författare)
- Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark.;Univ Copenhagen, Fac Med, Inst Clin Med, Copenhagen, Denmark
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- Nielsen, Rikke Linnemann (författare)
- Tech Univ Denmark, Dept Hlth Technol, DK-2800 Copenhagen, Denmark.;Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark.;Novo Nordisk Res Ctr Oxford, Oxford, England
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Tech Univ Denmark, Dept Hlth Technol, DK-2800 Copenhagen, Denmark;Univ Hosp, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark Vilnius Univ Hosp, Santaros Klin Ctr Pediat Oncol & Hematol, Vilnius, Lithuania.;Vilnius Univ, Vilnius, Lithuania (creator_code:org_t)
- 2022-03-22
- 2022
- Engelska.
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 69:6
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background White blood cell count (WBC) as a measure of extramedullary leukemic cell survival is a well-known prognostic factor in acute lymphoblastic leukemia (ALL), but its biology, including impact of host genome variants, is poorly understood.Methods We included patients treated with the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-2008 protocol (N = 2347, 72% were genotyped by Illumina Omni2.5exome-8-Bead chip) aged 1-45 years, diagnosed with B-cell precursor (BCP-) or T-cell ALL (T-ALL) to investigate the variation in WBC. Spline functions of WBC were fitted correcting for association with age across ALL subgroups of immunophenotypes and karyotypes. The residuals between spline WBC and actual WBC were used to identify WBC-associated germline genetic variants in a genome-wide association study (GWAS) while adjusting for age and ALL subtype associations.Results We observed an overall inverse correlation between age and WBC, which was stronger for the selected patient subgroups of immunophenotype and karyotypes (rho(BCP-ALL )= -.17, rho(T-ALL )= -.19; p < 3 x 10(-4)). Spline functions fitted to age, immunophenotype, and karyotype explained WBC variation better than age alone (rho = .43, p << 2 x 10(-6)). However, when the spline-adjusted WBC residuals were used as phenotype, no GWAS significant associations were found. Based on available annotation, the top 50 genetic variants suggested effects on signal transduction, translation initiation, cell development, and proliferation.Conclusion These results indicate that host genome variants do not strongly influence WBC across ALL subsets, and future studies of why some patients are more prone to hyperleukocytosis should be performed within specific ALL subsets that apply more complex analyses to capture potential germline variant interactions and impact on WBC.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Nyckelord
- acute lymphoblastic leukemia (ALL)
- genome-wide association studies (GWAS)
- genotype
- spline functions
- white blood cell count (WBC)
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- art (ämneskategori)
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Helenius, Marian ...
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Vaitkeviciene, G ...
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Abrahamsson, Jon ...
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Jonsson, Olafur ...
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Lund, Bendik
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Harila-Saari, Ar ...
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Vettenranta, Kim
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Mikkel, Sirje
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Stanulla, Martin
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Lopez-Lopez, Eli ...
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Waanders, Esme
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Madsen, Hans O.
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Marquart, Hanne ...
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Modvig, Signe
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Gupta, Ramneek
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Schmiegelow, Kje ...
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Nielsen, Rikke L ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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Uppsala universitet