title: Involvement of BAFF and APRIL in Resistance to Apoptosis of Acute Myeloid Leukemia.
abstract: B-cell activation factor of the TNF family (BAFF), and a proliferation-inducing ligand (APRIL), two members of the tumour necrosis factor (TNF) superfamily, beyond playing a significant role in normal B-cell development, promote survival and proliferation of malignant B cells. Both ligands interact with 3 receptors: BAFF-R, specific to BAFF, and TACI and BCMA which are shared by both BAFF and APRIL. Here we wished to investigate the potential role of these proteins in resistance of acute myeloid leukaemia (AML) blasts to apoptosis. We found that the levels of both mRNA and proteins of APRIL, BAFF and their receptors were expressed in leukaemic cells of 24 newly diagnosed, untreated AML patients. We also demonstrated that patients who did not further respond to induction therapy (NR) presented with significantly higher baseline APRIL and BAFF expression on AML blasts as compared to these subjects who, after induction, achieved complete remission (CR) following induction therapy. Moreover, we observed striking differences in baseline levels of BCMA between CR and NR patients as we did not find detectable expression of this receptor in the latter group of patients. Interestingly, we found that AML blasts collected at baseline from NR patients cultured in presence of exogenous BAFF and APRIL were significantly more resistant to spontaneous or drug-induced apoptosis as compared with cells derived from CR patients. Altogether, our data confirm that BAFF and APRIL signaling play important role in AML pathogenesis and susceptibility to cytotoxic therapy while measuring of BCMA expression on AML cells can become a novel prognostic factor for chemotherapy response.
authors.affiliation: Department of Haematology, Medical University of Bialystok, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Bolkun
authors.affiliation: Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Poland.
authors.forename: Kamil
authors.initials: K
authors.lastname: Grubczak
authors.affiliation: Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, KY, USA.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Schneider
authors.affiliation: Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Poland.
authors.forename: Paula
authors.initials: P
authors.lastname: Zembko
authors.affiliation: Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Radzikowska
authors.affiliation: Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Singh
authors.affiliation: Department of Haematology, Medical University of Bialystok, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Kloczko
authors.affiliation: Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, KY, USA.
authors.forename: Mariusz Z
authors.initials: MZ
authors.lastname: Ratajczak
authors.affiliation: Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Moniuszko
authors.affiliation: Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Eljaszewicz
keywords: APRIL; BAFF; BCMA; acute myeloid leukaemia; treatment response