6533b856fe1ef96bd12b2802

RESEARCH PRODUCT

The monocytic population in chronic lymphocytic leukemia shows altered composition and deregulation of genes involved in phagocytosis and inflammation.

Claudio TripodoStefania FiorcariJenny BulgarelliGiulia DebbiaPatrizia ZucchiniGoretta BonacorsiMario LuppiLinda BertoncelliFranco NarniRossana MaffeiSilvia MartinelliSilvia DeaglioSara De BiasiCarla GuarnottaRoberto MarascaIlaria CastelliAndrea Cossarizza

subject

AdultMaleCD14Chronic lymphocytic leukemiaPhagocytosisPopulationDown-RegulationInflammationMICROENVIRONMENTCD16BiologyTUMOR-ASSOCIATED MACROPHAGES; TIE2-EXPRESSING MONOCYTES; MICROENVIRONMENT; CLLMonocytesImmune systemPhagocytosismedicineHumanseducationCells CulturedAgedAged 80 and overInflammationeducation.field_of_studyMonocyteGene Expression ProfilingHematologyMiddle Agedmedicine.diseaseLeukemia Lymphocytic Chronic B-CellTIE2-EXPRESSING MONOCYTESGene Expression Regulation NeoplasticChronic Lymphocytic Leukemia; Monocyte; microenvironmentTUMOR-ASSOCIATED MACROPHAGESmedicine.anatomical_structureImmunologyFemalemedicine.symptomLymphocyte Culture Test MixedOriginal Articles and Brief ReportsCLL

description

Macrophages reside in tissues infiltrated by chronic lymphocytic leukemia B cells and the extent of infiltration is associated with adverse prognostic factors. We studied blood monocyte population by flow cytometry and whole-genome microarrays. A mixed lymphocyte reaction was performed to evaluate proliferation of T cells in contact with monocytes from patients and normal donors. Migration and gene modulation in normal monocytes cultured with CLL cells were also evaluated. The absolute number of monocytes increased in chronic lymphocytic leukemia patients compared to the number in normal controls (792 +/- 86 cells/mu L versus 485 +/- 46 cells/mL, P=0.003). Higher numbers of non-classical CD14(+)CD16(++) and Tie-2-expressing monocytes were also detected in patients. Furthermore, we performed a gene expression analysis of monocytes in chronic lymphocytic leukemia patients, showing up-regulation of RAP1GAP and down-regulation of tubulins and CDC42EP3, which would be expected to result in impairment of phagocytosis. We also detected gene alterations such as down-regulation of PTGR2, a reductase able to inactivate prostaglandin E2, indicating immunosuppressive activity. Accordingly, the proliferation of T cells in contact with monocytes from patients was inhibited compared to that of cells in contact with monocytes from normal controls. Finally, normal monocytes in vitro increased migration and up-regulated CD16, RAP1GAP, IL-10, IL-8, MMP9 and down-regulated PTGR2 in response to leukemic cells or conditioned media. In conclusion, altered composition and deregulation of genes involved in phagocytosis and inflammation were found in blood monocytes obtained from chronic lymphocytic leukemia patients, suggesting that leukemia-mediated "education" of immune elements may also include the establishment of a skewed phenotype in the monocyte/macrophage population.

yearjournalcountryeditionlanguage
2013-01-01Haematologica
10.3324/haematol.2012.073080https://pubmed.ncbi.nlm.nih.gov/23349302