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The human cathelicidin hCAP-18 in serum of children with haemato-oncological diseases
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Univ Childrens Hosp, Uppsala, Sweden..
Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden.;Univ Childrens Hosp, Uppsala, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Univ Childrens Hosp, Uppsala, Sweden..
Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Clin Genet, Stockholm, Sweden.;Univ Helsinki, Childrens Hosp, Pediat Res Ctr, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland..
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2022 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 198, no 6, p. 1023-1031Article in journal (Refereed) Published
Abstract [en]

The human cathelicidin hCAP-18 (pro-LL-37) is the pro-protein of the antimicrobial peptide LL-37. hCAP-18 can be produced by many different cell types; bone marrow neutrophil precursors are the main source of hCAP-18 in the circulation. Neutrophil count is used as a marker for myelopoiesis but does not always reflect neutrophil production in the bone marrow, and thus additional markers are needed. In this study, we established the reference interval of serum hCAP-18 level in healthy children and compared serum hCAP-18 levels between different diagnostic groups of children with haemato-oncological diseases, at diagnosis. We found that children with diseases that impair myelopoiesis, such as acute leukaemia, aplastic anaemia, or myelodysplastic syndrome, presented with low hCAP-18 levels, whereas patients with non-haematological malignancies displayed serum hCAP-18 levels in the same range as healthy children. Children with chronic myeloid leukaemia presented with high circulating levels of hCAP-18, probably reflecting the high number of all differentiation stages of myeloid cells. We suggest that analysis of serum hCAP-18 provides additional information regarding myelopoiesis in children with haemato-oncological diseases, which may have future implications in assessment of myelopoiesis in clinical management.

Place, publisher, year, edition, pages
Wiley John Wiley & Sons, 2022. Vol. 198, no 6, p. 1023-1031
Keywords [en]
aplastic anaemia, cathelicidin, hCAP-18, leukaemia, myelopoiesis, paediatric cancer
National Category
Hematology
Identifiers
URN: urn:nbn:se:uu:diva-492729DOI: 10.1111/bjh.18360ISI: 000826602800001PubMedID: 35849644OAI: oai:DiVA.org:uu-492729DiVA, id: diva2:1725223
Funder
Swedish Childhood Cancer Foundation, ST2013-0008Swedish Childhood Cancer Foundation, TJ2020-0069Available from: 2023-01-10 Created: 2023-01-10 Last updated: 2024-01-15Bibliographically approved
In thesis
1. Vitamin D, bone turnover markers and hCAP-18 in children with hemato-oncological diseases
Open this publication in new window or tab >>Vitamin D, bone turnover markers and hCAP-18 in children with hemato-oncological diseases
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Children with hemato-oncological diseases may have significant skeletal morbidities. Vitamin D is essential for the maintenance of skeletal health and may also be important for immunological functions and cancer outcomes. As vitamin D deficiency is a recognized problem in children worldwide, it is important to evaluate its prevalence among children and adolescents with hemato-oncological diseases in Sweden.

In this thesis, I investigated vitamin D status and its predictors, serum hCAP-18 (the pro-protein of the antimicrobial peptide LL-37 produced during neutrophil differentiation in the bone marrow), and bone turnover markers in children with hemato-oncological diseases at the time of diagnosis. 

Vitamin D deficiency was found in 30.9–46% of the children. Lower 25-hydroxyvitamin D level correlated with older age, seasons outside summer, a more recent calendar year of sampling, lack of vitamin D supplementation, and country of parental origin located between latitudes -45° and 45°. In preschool children with leukemia, a 25-hydroxyvitamin D level < 50 nmol/L was associated with inferior overall survival. 

There was no correlation between serum 25-hydroxyvitamin D and hCAP-18 neither in children with hemato-oncological diseases nor in healthy controls. Children with diseases that impair myelopoiesis presented low hCAP-18 levels, whereas those with non-hematological malignancies displayed serum hCAP-18 levels in the same range as that of healthy children.

Children diagnosed with leukemia had lower levels of bone formation and resorption markers than those of children with solid tumors or bone marrow failure. Adolescents with osteosarcoma displayed high bone alkaline phosphatase levels.

The identification of patients with suboptimal vitamin D status and compromised bone remodeling at cancer diagnosis may aid the development of supportive treatments that reduce the adverse effects of cancer and its treatment. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2023. p. 61
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1938
Keywords
vitamin D, pediatric cancer, leukemia, bone marrow failure, hCAP-18, bone turnover markers
National Category
Pediatrics
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-499601 (URN)978-91-513-1785-4 (ISBN)
Public defence
2023-05-24, Rudbecksalen, Rudbeck Laboratory, Dag Hammarskjölds väg 20, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Funder
Swedish Childhood Cancer Foundation, TJ2020-0069, ST2013-0008
Available from: 2023-05-02 Created: 2023-04-02 Last updated: 2026-04-24

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Jackmann, NataljaFrisk, PerHarila-Saari, Arja H.

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Jackmann, NataljaFrisk, PerUtriainen, PauliinaHarila-Saari, Arja H.
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