Publications by authors named "Djamel Aggoune"
Article Synopsis
- The study investigates how leukemic cells find refuge in the bone marrow and the role of specific adhesion molecules, CD44 and E-selectin, in chronic myeloid leukemia (CML).
- Researchers hypothesized that inhibiting the adhesion of CML-initiating cells to the bone marrow's E-selectin could enhance the effectiveness of imatinib treatment, and found that combining the E-selectin inhibitor GMI-1271 with imatinib improved survival in mice by reducing leukemic cell interactions with the bone marrow.
- The findings suggest that targeting specific molecular pathways, such as the modulation of adhesion molecules like CD44 and the phosphorylation of SCL/TAL1, could lead to better treatment strategies for CML in humans
Article Synopsis
- - SOD2 is important for antioxidant defense, and this study investigates its potential link to genetic instability in Chronic Myeloid Leukemia (CML), specifically how silencing SOD2 affects chromosomal stability in cell lines expressing BCR-ABL mutations.
- - Researchers found that SOD2 silencing led to significant genetic instability in specific chromosomal regions and observed lower SOD2 mRNA levels in CML patients, correlating with increased disease severity indicators like leukocytosis and Sokal score.
- - The study suggests that reduced SOD2 expression may contribute to a mutator phenotype in CML patients undergoing Tyrosine Kinase Inhibitor (TKI) therapies, highlighting the need for further research into
Although it has been well-demonstrated that bone marrow mesenchymal stromal cells (MSCs) from CML patients do not belong to the Ph1-positive clone, there is growing evidence that they could play a role in the leukemogenesis process or the protection of leukemic stem cells from the effects of tyrosine kinase inhibitors (TKIs). The aim of the present study was to identify genes differentially expressed in MSCs isolated from CML patients at diagnosis (CML-MSCs) as compared to MSCs from healthy controls. Using a custom gene-profiling assay, we identified six genes over-expressed in CML-MSCs (BMP1, FOXO3, MET, MITF, NANOG, PDPN), with the two highest levels being documented for PDPN (PODOPLANIN) and NANOG.
View Article and Find Full Text PDFBCR-ABL induces an intrinsic genetic instability in chronic myeloid leukemia (CML). The protein breast cancer 1, early onset (BRCA1)-associated protein 1 (BAP1) is a deubiquitinase interacting with the DNA repair regulator BRCA1 and is frequently inactivated in many cancers. Here, we report that BAP1 mRNA and protein levels are downregulated in a BCR-ABL1-expressing hematopoietic cell line (UT-7/11).
View Article and Find Full Text PDFTyrosine kinase inhibitors (TKIs) have profoundly changed the natural history of chronic myeloid leukemia (CML). However, acquired resistance to imatinib, dasatinib or nilotinib (1(st) and 2(nd) generation TKIs), due in part to BCR-ABL1 kinase mutations, has been largely described. These drugs are ineffective on the T315I gatekeeper substitution, which remains sensitive to 3(rd) generation TKI ponatinib.
View Article and Find Full Text PDFThe physiological hematopoietic niche located in bone marrow is a pluricellular structure whose components are now well identified. Within this microenvironment, hematopoietic stem cells are in direct contact with mesenchymal stromal cells, osteoblasts and sinusoidal endothelial cells. These close relationships drive specialized cellular functions (proliferation/quiescence, differentiation/self-renewal) ensuring an efficient hematopoiesis.
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