Project description:Alterations of TWIST-1 expression are often seen in solid tumors and contribute to tumorigenesis and cancer progression. However, studies concerning its pathogenic role in leukemia are scarce. Here we show that TWIST-1 is a new candidate gene contributing to leukemogenesis of myeloid leukemia. We used array as one tool to determine gene expression profiles of control and TWIST-1-overexpressing U937 cells.
Project description:miRNA microarray expression analysis of human acute myeloid leukemia cell line (U937) after HDAC2 genetically and enzymatically defection
Project description:To investigate the molecular mechanism of matrine's anti-myeloid leukemia effect, Acute myeloid leukemia cells HL-60 and U937 and chronic myeloid leukemia cells K562 were treated with 0.8mg/mL matrine for 30min and 24h, respectively. Then, RNA-Seq data before and after matrine treatment were used for gene expression profile analysis
Project description:Acute myeloid leukemia (AML) and acute T-lymphoblastic leukemia (T-ALL) maintain the undifferentiated phenotype and proliferative capacity of their respective cells of origin, hematopoietic stem/progenitor cells and immature thymocytes. The mechanisms that maintain these progenitor-like characteristics are poorly understood. We report that transcription factor Zfx is required for the development and propagation of experimental AML caused by MLL-AF9 fusion, and of T-ALL caused by Notch1 activation. In both leukemia types, Zfx activated progenitor-associated gene expression programs and prevented differentiation. Key Zfx target genes included mitochondrial enzymes Ptpmt1 and Idh2, whose overexpression partially rescued the propagation of Zfx-deficient AML. These studies identify a common mechanism that controls the cell-of-origin characteristics of acute leukemias derived from disparate lineages and transformation mechanisms. Analysis of genomic ZFX binding in the AML cell line NOMO-1 and the T-ALL cell line RPMI-8402
Project description:Validation of a custom low density microarray. Gene expression differences were analysed in the following groups of blood samples and cell lines:<br>Two haematological neoplasia cell lines: U937 (promonocytic lymphoma) versus Jurkat (T leukemia).<br>Different types of haematological neoplasias: healthy donors, B-CLL patients, myeloid leukemia patients and U937 and Jurkat cell cultures samples.<br>Two hematological neoplasia with different origin (lymphoid for B-CLL and myeloid for the myeloid group).<br>Two types of myeloid leukemias (Acute myeloid leukemia and myelodisplastic syndrome).<br>B-CLL patients with different clinical behaviour.<br>Healthy donors and B-CLL patients.<br><br>Normalization was performed using two different methods, robust quantile normalization (QRN) and variance stabilization normalization (VSN), so that a set of statistcially significant probes found using both methods could be obtained.
Project description:The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feed-forward loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU.1. In the context of Hoxa9 overexpression, Syk induces Meis1, recapitulating several leukemogenic features of Hoxa9/Meis1-driven leukemia. Finally, we show that Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia.
