title: Childhood acute lymphoblastic leukemia (ALL) presenting with severe osteolysis: a model to study leukemia-bone interactions and potential targeted therapeutics.
abstract: Interference with the molecular mechanisms that generate tumor supportive niches in the bone microenvironment is a rational approach to inhibit the growth of hematological malignancies. However, the advancement of knowledge in this area has been slowed down by the lack of in vitro models to facilitate the screening of potential candidate agents. The rare cases of acute lymphoblastic leukemia (ALL) in children presenting with extensive bone involvement may represent an exaggerated form of some aspects of the normal tumor-bone interactions. Thus, these cases can provide insight into processes that are otherwise challenging to uncover. The authors describe the case of a 6-year-old child who presented with severe osteopenia that resolved at the time of leukemic remission. Compared to control sera, serum taken at disease presentation contained increased levels of a group of osteolytic cytokines and was effective in activating preosteoclast cells in culture. Based on these findings, the authors describe an experimental model to identify agents that would interfere with leukemia mediated osteolytic process.
authors.affiliation: Hughes Children's Cancer Research Centre, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Aarthi
authors.initials: A
authors.lastname: Jayanthan
authors.forename: Paivi M H
authors.initials: PM
authors.lastname: Miettunen
authors.forename: Andrea
authors.initials: A
authors.lastname: Incoronato
authors.forename: Clara L
authors.initials: CL
authors.lastname: Ortiz-Neira
authors.forename: Victor A
authors.initials: VA
authors.lastname: Lewis
authors.forename: Ronald
authors.initials: R
authors.lastname: Anderson
authors.forename: Dean E C
authors.initials: DE
authors.lastname: Frohlich
authors.forename: Aru
authors.initials: A
authors.lastname: Narendran
mesh_terms: D001851:Bone Diseases, Metabolic / Q000209:etiology*; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D010010:Osteoclasts / Q000502:physiology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000150:complications* / Q000188:drug therapy
chemical_list: D016207:Cytokines; D066246:ErbB Receptors