Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

Characteristics of white blood cell count in acute lymphoblastic leukemia: A COST LEGEND phenotype-genotype study

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Socioeconomic position and maintenance therapy in children with acute lymphoblastic leukemia: A national cohort study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Clinical evidence for a biological effect of epigenetically active decitabine in relapsed or progressive rhabdoid tumors

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Anti-CD19 CAR T cells administration was feasible in a child with primary hepatitis B infection

    Publikation: Bidrag til tidsskriftLetterForskningpeer review

  1. Socioeconomic position and maintenance therapy in children with acute lymphoblastic leukemia: A national cohort study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Life-threatening viral disease in a novel form of autosomal recessive IFNAR2 deficiency in the Arctic

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Asparaginase encapsulated in erythrocytes as second-line treatment in hypersensitive patients with acute lymphoblastic leukaemia

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Recurrent Germline Variant in RAD21 Predisposes Children to Lymphoblastic Leukemia or Lymphoma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

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 (ρBCP-ALL = -.17, ρT-ALL = -.19; p < 3 × 10-4 ). Spline functions fitted to age, immunophenotype, and karyotype explained WBC variation better than age alone (ρ = .43, p << 2 × 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.

OriginalsprogEngelsk
Artikelnummere29582
TidsskriftPediatric Blood & Cancer
Vol/bind69
Udgave nummer6
Sider (fra-til)e29582
ISSN1545-5009
DOI
StatusUdgivet - jun. 2022

Bibliografisk note

© 2022 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.

ID: 78117769