title: Prognostic significance of ligands belonging to tumour necrosis factor superfamily in acute lymphoblastic leukaemia.
abstract: Altered activities of ligands belonging to tumour necrosis factor (TNF) superfamily, namely B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and apoptosis inducing ligand (TRAIL) were demonstrated in several haematological diseases including acute lymphoblastic leukaemia (ALL). BAFF, APRIL and TRAIL provide crucial survival signals to immature, naive and activated B cells. These ligands are capable of activating a broad spectrum of intracellular signalling cascades that can either induce apoptosis or protect from programmed cell death. BAFF and APRIL, which can directly activate the NF-κB pathway, have been identified as crucial survival factors for ALL cells. Here, we have analyzed serum BAFF, APRIL and TRAIL concentrations in 48 patients with newly diagnosed ALL and 44 healthy volunteers. The levels of APRIL and BAFF were significantly higher in ALL patients as compared to healthy volunteers. In contrast, concentrations of TRAIL were significantly lower in ALL patients. Moreover, following induction, the levels of APRIL, but not BAFF or TRAIL, were significantly lower in a group of patients with complete remission (CR) as compared to non-respondent (NR) ALL patients. Furthermore, we demonstrated statistically significant differences in concentrations of APRIL between CR MRD-negative and CR, MRD-positive ALL patients. Notably detection of higher concentrations of APRIL was associated with shorter leukaemia-free survival and overall survival. Altogether, our data indicate that APRIL can play an important role in the pathogenesis of ALL and the measurement of APRIL levels can improve prognostication in ALL patients.
authors.affiliation: Department of Haematology, Medical University of Bialystok, Poland. Electronic address: lbolkun@gmail.com.
authors.forename: L
authors.initials: L
authors.lastname: Bolkun
authors.affiliation: Department of Haematology, Medical University of Bialystok, Poland; Department of Human Anatomy, Medical University of Bialystok, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Lemancewicz
authors.affiliation: Department of Immunology, Medical University of Bialystok, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Jablonska
authors.affiliation: Department of Haematology, Medical University of Bialystok, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Szumowska
authors.affiliation: Department of Pharmaceutical Technology, Medical University of Bialystok, Poland.
authors.forename: U
authors.initials: U
authors.lastname: Bolkun-Skornicka
authors.affiliation: Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Poland; Department of Allergology and Internal Medicine, Medical University of Bialystok, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Moniuszko
authors.affiliation: Department of Human Anatomy, Medical University of Bialystok, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Dzieciol
authors.affiliation: Department of Haematology, Medical University of Bialystok, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Kloczko
mesh_terms: D000293:Adolescent; D000328:Adult; D053264:B-Cell Activating Factor / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D011379:Prognosis; D015996:Survival Rate; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000097:blood*; D055815:Young Adult
chemical_list: D053264:B-Cell Activating Factor; D014408:Biomarkers, Tumor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C114631:TNFSF13 protein, human; C505719:TNFSF13B protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13
keywords: APRIL; Acute lymphoblastic leukaemia; BAFF; TRAIL