AML with mutated NPM1 usually carries normal karyotype (NK) but it may harbor chromosomal aberrations whose significance remains unclear. We addressed this question in 631 AML patients with mutated/cytoplasmic NPM1. An abnormal karyotype (AK) was present in 93/631 cases (14.7%), the most frequent abnormalities being +8, +4, -Y, del(9q), +21. Chromosome aberrations in NPM1-mutated AML were similar to, but occurred less frequently than additional chromosome changes found in other AML with recurrent cytogenetic abnormalities according to WHO classification. Four of the 31 NPM1-mutated AML patients karyotyped at different time points had NK at diagnosis but AK at relapse: del(9q) (n=2), t(2;11) (n=1), inv(12) (n=1).
AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features.
No sample metadata fields
View SamplesThe mechanisms that allow breast cancer cells to metabolically sustain growth are poorly understood. In breast cancer, FoxA1 transcription factor, along with estrogen receptor, regulates luminal cell specification and proliferation. Here we report that FoxA transcription factor family members FoxA1 and FoxA2 fuel cellular growth in breast cancer through the expression of a common target gene, namely the endothelial lipase (LIPG)
FoxA and LIPG endothelial lipase control the uptake of extracellular lipids for breast cancer growth.
Cell line
View SamplesThe transcription factor MEF2C is specifically induced by VEGF in endothelial cells. To delineate target genes of MEF2C in endothelial cells, which might be important during angiogenesis also, MEF2C was overexpressed adenovirally in human umbilical vein endothelial cells (HUVECs) over a period of 8 to 32 hours.
The transcription factor MEF2C negatively controls angiogenic sprouting of endothelial cells depending on oxygen.
Specimen part, Treatment
View SamplesWe show the molecular and functional characterization of a novel population of lineage-negative CD34-negative (Lin- CD34-) hematopoietic stem cells (HSCs) from chronic myelogenous leukemia (CML) patients at diagnosis. Molecular caryotyping and quantitative analysis of BCR/ABL transcript demonstrated that about one third of CD34- was leukemic. CML CD34- cells showed kinetic quiescence and limited clonogenic capacity. However, stroma-dependent cultures and cytokines induced CD34 expression on some HSCs, cell cycling, acquisition of clonogenic activity and increased expression of BCR/ABL transcript. CML CD34- cells showed an engraftment rate in immunodeficient mice similar to that of CD34+ cells. Gene expression profiling revealed the down-regulation of cell cycle arrest genes together with genes involved in antigen presentation and processing, while the expression of angiogenic factors was strongly up-regulated when compared to normal counterparts. Flow cytometry analysis confirmed the significant down-regulation of HLA class I and II molecules in CML CD34-cells. Increasing doses of imatinib mesilate (IM) did not affect fusion transcript levels, BCR-ABL kinase activity and the clonogenic efficiency of CML CD34- cells as compared to leukemic CD34+cells.
Molecular and functional analysis of the stem cell compartment of chronic myelogenous leukemia reveals the presence of a CD34- cell population with intrinsic resistance to imatinib.
No sample metadata fields
View SamplesThe goal of the study was to evaluate the influence of mutations in MLK4 on the protein function and the process of tumorigenesis in colorectal cancers. Biochemical data imply that a majority of MLK4 mutations in colon cancer are loss-of-function, including, E314K and Y330H mutations.
Recurrent MLK4 Loss-of-Function Mutations Suppress JNK Signaling to Promote Colon Tumorigenesis.
Specimen part, Cell line
View SamplesThalidomide-dexamethasone (TD) combination is an effective induction therapy for newly diagnosed multiple myeloma patients, candidates for subsequent autologous stem cell transplantation (ASCT). Since maximization of tumor response before ASCT may favorably affect the clinical outcomes, we designed a study to identify a gene expression profile (GEP) signature predictive of attainment of complete response to TD induction therapy. CD138+ bone marrow samples obtained at diagnosis from 112/311 patients were analyzed. Two subsequent time phases were planned. Firstly, a GEP supervised analysis, performed on a training set of 32 patients, allowed to identify 157 probe sets differentially expressed in complete responder + near complete responder (CR+nCR) versus partial responder patients. Than, we generated an 8-gene GEP signature predicting at diagnosis the probability to achieve CR+nCR to TD induction therapy. The performance of this assay was subsequently validated in an 80 patients training set. The 8-gene signature provide a negative predictive value of 93% and a positive predictive value of 44%. The 8 genes were down-regulated in patients who achieved at least a nCR. These results could be an important first step to adopting a diagnostic assay, used to determine, at diagnosis, patients who will respond more favourably to a particular treatment strategy.
Correlation between eight-gene expression profiling and response to therapy of newly diagnosed multiple myeloma patients treated with thalidomide-dexamethasone incorporated into double autologous transplantation.
Age, Specimen part, Disease, Disease stage
View SamplesAngiogenesis is defined as the formation of new capillaries by sprouting from preexisting vessels. It is mainly triggered by vascular endothelial growth factor (VEGF) and occurs in the adult primarily in wound healing processes or in pathologic tumor vessel growth. To identify genes specifically triggered by VEGF and involved in the process of angiogenesis, we utilized Affymetrix microarrays hybridized with cRNA of human umbilical vein endothelial cells (HUVEC) stimulated with either the main trigger of angiogenesis, VEGF or a more general mitogenic growth factor, EGF.
The VEGF-induced transcriptional response comprises gene clusters at the crossroad of angiogenesis and inflammation.
No sample metadata fields
View SamplesAngiogenesis, the formation of new capillaries by sprouting from preexisting vessels, is mainly induced by VEGF-A. To identify genes which are induced by VEGF-A in endothelial cells, HUVEC were starved and induced by VEGF-A165 for 30, 60 and 150min. RNA of induced and uninduced cells was isolated and subjected to microarray analysis using Affymetrix microarray.
The VEGF-induced transcriptional response comprises gene clusters at the crossroad of angiogenesis and inflammation.
Specimen part, Treatment, Time
View SamplesAnalysis of root gene expression of salt-tolerant genotypes FL478, Pokkali and IR63731, and salt-sensitive genotype IR29 under control and salinity-stressed conditions during vegetative growth. Results provide insight into the genetic basis of salt tolerance in indica rice.
Root-specific transcript profiling of contrasting rice genotypes in response to salinity stress.
No sample metadata fields
View SamplesGene expression profile of the response to chronic constant hypoxia in the heart of adult zebrafish
Transcriptome analysis of the response to chronic constant hypoxia in zebrafish hearts.
No sample metadata fields
View Samples