ABSTRACT: PAX5, a transcription factor essential for B-cell development, has been found as a frequent target of abnormalities in B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) cases, showing point mutations, deletions, as well as translocations with several partner genes. We identified four novel PAX5 fusion partner genes by performing a screening on BCP-ALL cases with 9p rearrangements. Copy Number Variation analysis of translocated samples showed that few significant cooperative genetic lesions are present in addition to the translocation event, suggesting that it might have a primary role in leukemogenesis.
Project description:The objective of the study was to investigate the extent of duplicated, triplicated, and quadruplicated regions in PMD patients so that junction analysis could be performed. 4 samples were analyzed. Replicates are not included.
Project description:Our study provides evidence that JAK2, PDL1 and PDL2 are recurrently affected by structural and numerical aberrations in lymphoid neoplasms. The study highlights the role of PDL1/PDL2 in lymphoma progression. single case analysis
Project description:We performed genomic and transcriptomic analysis of seven cases of molecular Burkitt lymphoma (mBL) developed in immunosuppressed patients who underwent solid organ transplantation. Interestingly, three cases (43%) were MYC-translocation-negative and revealed the 11q-gain/loss aberration recently identified in 3% of mBL developed in immunocompetent hosts.1 Based on array CGH data, minimal gain and loss regions of 11q (MGR/~4Mb and MLR/~13.5Mb, respectively) were defined and integrative genomic and transcriptomic analysis identified 35 differentially expressed genes, when compared with classic BL. All 16 MGR-dysregulated genes were upregulated, including cancer related USP2, CBL and PAFAH1B2. As expected, all 19 MGL-dysregulated genes were downregulated and two of them, TBRG1 and EI24, are potential tumor suppressor genes. Interestingly, the vast majority of dysregulated 11q23-q25 genes are involved in the MYC and TP53 networks. We hypothesize that the 11q-gain/loss aberration represents a “molecular variant” of t(8q24/MYC) and affects the same pathological pathways as the MYC oncogene. Seven cases of PTLD with BL features were selected from a cohort of 174 posttransplant patients diagnosed with PTLD between 1989 and 2012 at the University Hospitals of KU Leuven (Leuven, Belgium). In addition, five classic BL cases were selected as immunocompetent controls (IC-BL). Morphologic, immunophenotypic, clinical and cytogenetic characteristics of the selected cases were reviewed.
Project description:The aim of this study was to identify genes differentially expressed between the stem cell populations in BCP ALL, T ALL and normal healthy donors. In addition broad differences between healthy individuals or HSC and cell obtained from BCP ALL or T-ALL patients were also identified.
Project description:B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous disease that can be subdivided according to primary recurrent genetic abnormalities that are strongly associated with characteristic biological and clinical features. The detection of these abnormalities can facilitate diagnosis, risk stratification, and targeted therapy. We identified an unexpectedly high incidence of fusion genes involving ZNF384 genes, including TCF3-ZNF384, EP300-ZNF384, and CREBBP-ZNF384, in BCP-ALL of our cohort. We therefore used microarrays to evaluate the gene-expression characteristics of BCP-ALL harboring ZNF384-related fusion genes and compared with those of BCP-ALL with other types of conventional genetic abnormality. Overall design: BCP-ALL samples with various genetic abnormalities were selected for RNA extraction and hybridization on Affymetrix microarrays. In addition to BCP-ALL harboring ZNF384-related fusion genes, including TCF3-ZNF384 (10 cases), EP300-ZNF384 (5 cases), and CREBBP-ZNF384 (2 cases), BCP-ALL with conventional genetic abnormalities, such as BCR-ABL1 (19 cases), ETV6-RUNX1 (70 cases), high hyperdiploid (90 cases), MLL-AF4 (13 cases), and TCF3-PBX1 (19 cases), were included. As a control, non-leukemic B-cell precursor samples (3 cases) were also selected.
Project description:In vitro mix of DNA from patient-matched lung cancer and blood cell lines, representing 30,50,70,100% tumor cell tissue, analyzed on Affymetrix 6.0 arrays. Lung cancer cell line H-1395 and patient-matched blood cell line BL1395 were obtained from ATCC and cultured according to their recommendations. DNA extraction was performed using the DNeasy Tissue Kit (Qiagen, Hilden, Germany). DNA from patient-matched Lung cancer and Blood cell lines NCI-H1395 and NCI-BL1395 were mixed to simulate tumor tissue with 30,50,70,100% cancer cells. The DNA ratio was adjusted to compensate for NCI-H1395 being nearly triploid. DNA was analyzed on Affymetrix SNP6.0 microarrays according to the manufacturer's protocol.
Project description:We studied the in vitro and in vivo efficacy of the HDAC inhibitor Givinostat/ITF2357 in BCP-ALL with CRLF2 rearrangements. We used BCP-ALL CRLF2- rearranged MHH-CALL4 and MUTZ5 cell lines as well as blasts from CRLF2 rearranged BCP-ALL patients and patients’ derived xenograft samples. We conclude that Givinostat may represent a novel and effective tool, in combination with current chemotherapy, to treat this subsets of ALL with poor prognosis and chemotherapy-related toxicity. Overall design: Gene expression was measured using Affymetrix platform in 5 pair of BCP-ALL patient derived xenograft samples treated or untreated ex vivo with Givinostat at 0.2 uM for 6 hours.
Project description:Chromosomal aberrations were studied both in a lung cancer cell line and colorectal cancer tumor samples. Results were verified by SKY karyotypes and by DNA ploidy analysis. The sensitivity of detecting chromosomal aberrations in tumor samples was evaluated by analyzing data from simulated mixtures of the lung cancer cell line H1395 and the normal cell line 1395BL from the same patient. Copy number analysis is presented on 12 colorectal cancer tumor samples and on in silico dilutions of a lung cancer cell line and its patient-matched blood cell line.