6533b855fe1ef96bd12b12c9
RESEARCH PRODUCT
Functional Activation of Osteoclast Commitment in Chronic Lymphocytic Leukaemia: A Possible Role for RANK/RANKL Pathway
Davide BagnaraDavide BagnaraAdalberto IbaticiDaniela De ToteroMichele PennonePaolo GiannoniAlessandro BelliniAnna Maria OrengoMichele PianaMaurizio MiglinoHülya EfetürkFrancesca La RosaElena GugiattiMichele CilliFrancesco FizCecilia MariniAlberto NieriFranco FaisValerio BrucatoLaura EmioniteGiovanna CutronaElisabetta TedoneCristina CampiCarlo Emanuele NeumaierAnna Maria MassoneSilvia BrunoSerena MatisAnna BorraRoberta PivaGianmario SambucetiMatteo BaucknehtClaudya TencaPaolo Bruzzisubject
Male0301 basic medicineChronic lymphocytic leukaemiaClone (cell biology)Osteoclastslcsh:MedicineMice0302 clinical medicineMice Inbred NODBone MarrowPositron Emission Tomography Computed Tomographyhemic and lymphatic diseases80 and overProspective StudiesChroniclcsh:ScienceAged 80 and overSettore ING-IND/24 - Principi Di Ingegneria ChimicaLeukemiaMultidisciplinaryBone Density Conservation AgentsReceptor Activator of Nuclear Factor-kappa BbiologyMiddle AgedLymphocyticLeukemiamedicine.anatomical_structureDenosumabRANKL030220 oncology & carcinogenesisFemaleDenosumabmedicine.drugAdultStromal cellArticle03 medical and health sciencesOsteoclastmedicineAnimalsHumansAgedRANK/RANKL Pathwaybusiness.industryRANK Ligandlcsh:RB-CellDiagnostic markersRANK LigandAdult; Aged; Aged 80 and over; Animals; Bone Density Conservation Agents; Bone Marrow; Denosumab; Female; Glucose; Humans; Leukemia Lymphocytic Chronic B-Cell; Male; Mice Inbred NOD; Middle Aged; Osteoclasts; Positron Emission Tomography Computed Tomography; Prospective Studies; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Xenograft Model Antitumor Assaysmedicine.diseaseLeukemia Lymphocytic Chronic B-CellXenograft Model Antitumor AssaysGlucose030104 developmental biologyChronic Lymphocytic Leukaemiabiology.proteinCancer researchInbred NODlcsh:QBone marrowbusinessdescription
AbstractSkeletal erosion has been found to represent an independent prognostic indicator in patients with advanced stages of chronic lymphocytic leukaemia (CLL). Whether this phenomenon also occurs in early CLL phases and its underlying mechanisms have yet to be fully elucidated. In this study, we prospectively enrolled 36 consecutive treatment-naïve patients to analyse skeletal structure and bone marrow distribution using a computational approach to PET/CT images. This evaluation was combined with the analysis of RANK/RANKL loop activation in the leukemic clone, given recent reports on its role in CLL progression. Bone erosion was particularly evident in long bone shafts, progressively increased from Binet stage A to Binet stage C, and was correlated with both local expansion of metabolically active bone marrow documented by FDG uptake and with the number of RANKL + cells present in the circulating blood. In immune-deficient NOD/Shi-scid, γcnull (NSG) mice, administration of CLL cells caused an appreciable compact bone erosion that was prevented by Denosumab. CLL cell proliferation in vitro correlated with RANK expression and was impaired by Denosumab-mediated disruption of the RANK/RANKL loop. This study suggests an interaction between CLL cells and stromal elements able to simultaneously impair bone structure and increase proliferating potential of leukemic clone.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-10-01 |