title: Asparagine and aspartic acid concentrations in bone marrow versus peripheral blood during Berlin-Frankfurt-Münster-based induction therapy for childhood acute lymphoblastic leukemia.
abstract: A recent study suggested that mesenchymal cells in bone marrow (BM) may counteract l-asparaginase (L-Asp)-containing acute lymphoblastic leukemia (ALL) therapy by secreting asparagine. Herein, we compared asparagine and aspartic acid concentrations in the BM and peripheral blood (PB), in order to determine whether this in vitro observation could be translated into in vivo differences of amino acid levels between both compartments. Asparagine and aspartic acid concentrations in BM (days 15 and 33) and PB (days 12, 15 and 33) were measured during L-Asp-containing Berlin-Frankfurt-Münster (BFM)-based 5-week multi-agent remission induction therapy in 11 children diagnosed with ALL at the St. Anna Children's Hospital in Vienna, Austria. The level of asparagine depletion did not differ significantly between both compartments at any time point measured, but aspartic acid concentrations were significantly higher in BM than PB at days 15 and 33 (p < 0.05). In the context of the reported mesenchymal asparagine production in BM, an increased asparagine production may indeed take place in BM. However, it may be overcome by continuous action of L-Asp, which is mirrored by increased aspartic acid levels but unchanged low asparagine levels in BM, suggesting a higher BM turnover of asparagine generated by L-Asp during induction therapy.
authors.affiliation: Department of Pediatric Hematology and Oncology, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: Manuel
authors.initials: M
authors.lastname: Steiner
authors.forename: Daniela
authors.initials: D
authors.lastname: Hochreiter
authors.forename: David C
authors.initials: DC
authors.lastname: Kasper
authors.forename: Rosa
authors.initials: R
authors.lastname: Kornmüller
authors.forename: Herbert
authors.initials: H
authors.lastname: Pichler
authors.forename: Oskar A
authors.initials: OA
authors.lastname: Haas
authors.forename: Ulrike
authors.initials: U
authors.lastname: Pötschger
authors.forename: Caroline
authors.initials: C
authors.lastname: Hutter
authors.forename: Michael N
authors.initials: MN
authors.lastname: Dworzak
authors.forename: Georg
authors.initials: G
authors.lastname: Mann
authors.forename: Andishe
authors.initials: A
authors.lastname: Attarbaschi
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage / Q000097:blood; D001216:Asparagine / Q000097:blood*; D001224:Aspartic Acid / Q000097:blood*; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D018698:Glutamic Acid / Q000097:blood; D005973:Glutamine / Q000097:blood; D006801:Humans; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy*; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000305:Adrenal Cortex Hormones; D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D014750:Vincristine; D001216:Asparagine; D001215:Asparaginase; D003630:Daunorubicin