title: Cytokines, growth, and environment factors in bone marrow plasma of acute lymphoblastic leukemia pediatric patients.
abstract: Acute lymphoblastic leukemia (ALL) cells depend on the microenvironment of the host in vivo and do not survive in in vitro culture. Conversely, the suppression of non-malignant tissues is one of the leading characteristics of the course of ALL. Both the non-malignant suppression and malignant cell survival may be partly affected by soluble factors within the bone marrow (BM) environment. Here, we aimed to identify proteins in BM plasma of children with ALL that may contribute to ALL aggressiveness and/or the microenvironment-mediated survival of ALL cells. LBMp (leukemic bone marrow plasma) at the time of ALL diagnosis was compared to control plasma of bone marrow (CBMp) or peripheral blood (CPBp) using a cytokine antibody array. The cytokine antibody array enabled simultaneous detection of 79 proteins per sample. Candidate proteins exhibiting significantly different profiles were further analyzed and confirmed by ELISA. mRNA expression of one of the candidate proteins (TIMP1) was studied using quantitative reverse transcriptase polymerase chain reaction (qRTPCR). The cytokine antibody array experiments identified 23 proteins that differed significantly (p<0.05); of these, two proteins (TIMP1 and LIF) withstood the Bonferroni correction. In contrast, little difference was observed between CBMp and CPBp. At the diagnosis of ALL, changes in the soluble microenvironment are detectable in BM plasma. These changes probably participate in the pathogenesis and/or result from the changes in the cell composition.
authors.affiliation: CLIP - Childhood Leukemia Investigation Prague, Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Kováč
authors.affiliation: CLIP - Childhood Leukemia Investigation Prague, Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Vášková
authors.affiliation: Institute of Microbiology v.v.i., Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Denisa
authors.initials: D
authors.lastname: Petráčková
authors.affiliation: CLIP - Childhood Leukemia Investigation Prague, Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Vendula
authors.initials: V
authors.lastname: Pelková
authors.affiliation: CLIP - Childhood Leukemia Investigation Prague, Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Ester
authors.initials: E
authors.lastname: Mejstříková
authors.affiliation: CLIP - Childhood Leukemia Investigation Prague, Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Kalina
authors.affiliation: CLIP - Childhood Leukemia Investigation Prague, Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Markéta
authors.initials: M
authors.lastname: Žaliová
authors.affiliation: Institute of Microbiology v.v.i., Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Weiser
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Starý
authors.affiliation: CLIP - Childhood Leukemia Investigation Prague, Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Hrušák
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D001853:Bone Marrow / Q000378:metabolism*; D002470:Cell Survival; D002648:Child; D016207:Cytokines / Q000097:blood*; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000096:biosynthesis*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000473:pathology; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D012333:RNA, Messenger; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1
keywords: bone marrow plasma; cytokine antibody array; pediatric acute lymphoblastic leukemia