title: Increased megakaryocytic proliferation, pro-platelet deposition and expression of fibrosis-associated factors in children with chronic myeloid leukaemia with bone marrow fibrosis.
abstract: Paediatric chronic myeloid leukaemia (ped-CML) is rare and ped-CML with fibre accumulation in the bone marrow (MF) is thought to be even rarer. In adults (ad-CML), fibrosis represents an adverse prognostic factor. So far, the pro-fibrotic changes in the bone marrow microenvironment have not been investigated in detail in ped-CML. From a total of 66 ped-CML in chronic phase, biopsies were analysable and 10 had MF1/2 (MF1, n=8/10; MF2, n=2/10). We randomly selected 16 ped-CML and 16 ad-CML cases with and without fibrosis (each n=8) as well as 18 non-neoplastic controls. Bone marrow samples were analysed with a real-time PCR-based assay (including 127 genes for paediatric cases) and by immunohistochemistry. We found increased expression of megakaryocytic genes in ped-CML. The number of megakaryocytes and pro-platelets are increased in CML patients, but the most significant increase was noted for ped-CML-MF1/2. Anti-fibrotic MMP9 expression was lower in children than in adults. Cell mobilisation-related CXCL12 was decreased in young and adult patients with CML but not the corresponding receptor CXCR4. In summary, fibre accumulation in ped-CML-MF1/2 is associated with increased megakaryocytic proliferation and increased interstitial pro-platelet deposition. Deregulated expression of matrix-modulating factors shifts the bone marrow microenvironment towards fibrosis.
authors.affiliation: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Hussein
authors.affiliation: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Stucki-Koch
authors.affiliation: Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Göhring
authors.affiliation: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Kreipe
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Suttorp
mesh_terms: D000293:Adolescent; D001792:Blood Platelets / Q000502:physiology*; D001853:Bone Marrow / Q000473:pathology*; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D005260:Female; D005355:Fibrosis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D008297:Male; D008533:Megakaryocytes / Q000473:pathology*; D035683:MicroRNAs / Q000032:analysis; D009154:Mutation; D059467:Transcriptome
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; C547183:MIRN10 microRNA, human; C542542:MIRN146 microRNA, human; D035683:MicroRNAs