Project description:3 patients with childhood acute lymphoblastic leukemia were diagnosed with relapsed, and the matched new diagnosed blood samples were enrolled as controls. CirRNA array were conducted for detecting the expression of miRNA in above samples.
Project description:3 patients with childhood acute lymphoblastic leukemia were diagnosed with relapsed, and the matched new diagnosed blood samples were enrolled as controls. MiRNA array were conducted for detecting the expression of miRNA in above samples.
Project description:<p>Although multi-agent combination chemotherapy is curative in a significant fraction of childhood acute lymphoblastic leukemia (ALL) patients, 20% of cases relapse and most die due to chemo-refractory disease. Here we used whole-exome and whole-genome sequencing to analyze the mutational landscape and pattern of clonal evolution at relapse in pediatric ALL cases. These analyses showed that ALL relapses originate from a common ancestral precursor clone of the diagnosis and relapsed populations and frequently harbor mutations implicated in chemotherapy resistance. RAS-MAPK pathway activating mutations in NRAS, KRAS and PTPN11 were present in 24/55 (44%) cases in our series. Notably, while some cases showed emergence of RAS mutant clones at relapse, in others, RAS mutant clones present at diagnosis were replaced by RAS wild type populations. Mechanistically, functional dissection of mouse and human wild type Kras and mutant Kras (Kras G12D) isogenic leukemia cells demonstrated induction of methotrexate resistance, but also improved response to vincristine, in mutant Kras- expressing lymphoblasts. These results identify chemotherapy driven selection as a central mechanism of leukemia clonal evolution and pave the road for the development of tailored personalized therapies for the treatment of relapsed ALL. </p>
Project description:B-cell acute lymphoblastic leukemia (B-ALL) is the most prevailing childhood cancer. As predicated by its prenatal origin, infant B-ALL (iB-ALL) show a silent mutational landscape irrespective of the MLL rearrangement/status, suggesting that other regulatory mechanisms might be impaired in the context of the disease. Here we used the most recent Illumina MethylationEPIC Beadchip platform to describe the genome-wide DNA methylation changes observed in a total of 69 de novo MLL-AF4+, MLL-AF9+ and non-rearranged MLL iB-ALL leukemias uniformly treated according to Interfant 99/06 protocol. Please note that samples X8 and X9 (pool of B cells and BCP) correspond to samples 200340580160_R08C01 and 200340580161_R07C01 from study E-MTAB-6315, respectively.
Project description:Retaining the mutational pattern of tumors, immortalized cell lines represent excellent tools for the molecular study of genetic aberrations. Tumors can consist of subclones which develop under selective forces driven by mutational alterations. This explains why after therapy, relapsed clones can be genetically distinct from clones at diagnosis. We analyzed the mutational patterns of pairs of cell lines raised at early and late phases of development from patients with a hematopoietic tumor named pre-B acute lymphoblastic leukemia (ALL). All cell lines tested showed mutations that typically occur in this tumor. We also observed clonal differences in sister cell lines, genetic aberrations developing during disease progression. Especially noteworthy was the presence of two mutations which are hitherto undescribed in cell lines.
Project description:Retaining the mutational pattern of tumors, immortalized cell lines represent excellent tools for the molecular study of genetic aberrations. Tumors can consist of subclones which develop under selective forces driven by mutational alterations. This explains why after therapy, relapsed clones can be genetically distinct from clones at diagnosis. We analyzed the mutational patterns of pairs of cell lines raised at early and late phases of development from patients with a hematopoietic tumor named pre-B acute lymphoblastic leukemia (ALL). All cell lines tested showed mutations that typically occur in this tumor. We also observed clonal differences in sister cell lines, genetic aberrations developing during disease progression. Especially noteworthy was the presence of two mutations which are hitherto undescribed in cell lines.
Project description:We investigated the chromatin accessibility landscape of normal T cells and T-Cell Acute Lymphoblastic Leukemia to define the thymocyte development using chromatin accessibility profiles and map the aberrant leukemia-associated accessibility sites in T-ALL.
Project description:This SuperSeries is composed of the following subset Series: GSE28460: Expression data from ALL diagnosis and relapse pediatric acute lymphoblastic leukemia cases GSE28461: Promoter methylation data from ALL diagnosis and relapse pediatric acute lymphoblastic leukemia cases Refer to individual Series