Project description:Acute megakaryoblastic leukemia (AMKL) is a heterogeneous disease generally associated with poor prognosis. Gene expression profiles indicate the existence of distinct molecular subgroups, and several genetic alterations have been characterized in the past years, including the t(1;22)(p13;q13) and the trisomy 21 associated with GATA1 mutations. However, the majority of patients do not present known mutations, and the limited access to primary patient leukemic cells impedes the efficient development of novel therapeutic strategies. In this study, using a xenotransplantation approach, we have modeled human pediatric AMKL in immunodeficient mice. Analysis of high-throughput RNA sequencing identified recurrent fusion genes defining new molecular subgroups.
Project description:The goal of this study is to define a gene expression signature unique to DS-AMKL (acute megakaryoblastic leukemia or FAB M7 leukemia). A similar study was done previously, but using unfractionated patient leukemic samples. In this study, we sorted megakaryocytic leukemia blasts from patients and then compared their gene expression signatures to those from similarly sorted blasts from patients with non-DS AMKL. This allowed us to identify a gene expression signature more unique to DS-AMKL samples.
Project description:In the previous studies, we reported that Mpl alternative splicing form Mpl-del overexpressed in acute megakaryoblasttic leukemia (AMKL) patients and mediated thrombopoietin signaling to promote AMKL cells malignant proliferation and chemotherapy resisitance. To investigate the detailed mechanism of Mpl-del mediated AMKL cells proliferation and survival, the AMKL cell Dami stably expressing GFP or Mpl-del-GFP were established by transduction with GFP or Mpl-del-GFP lentiviruses and treated with 20ng/ml TPO for RNA-SEQ analysis to examine the expression of proliferation and survival-related genes. Our results indicated that the levels of the "leading edge" genes that account for survival and prolieration were significantly higher in Mpl--del overexpressed AMKL cells.
Project description:The goal of this study is to define a gene expression signature unique to DS-AMKL (acute megakaryoblastic leukemia or FAB M7 leukemia). A similar study was done previously, but using unfractionated patient leukemic samples. In this study, we sorted megakaryocytic leukemia blasts from patients and then compared their gene expression signatures to those from similarly sorted blasts from patients with non-DS AMKL. This allowed us to identify a gene expression signature more unique to DS-AMKL samples. The leukemic blasts were sorted based on CD41, CD7, CD117, CD33, and CD34 antibodies as previously described (Klin. Padiatr. 217, 126-134).
Project description:The goal of this study is to define miR-125b-2 target genes in the hematopoietic system by genetic alteration of miR-125b expression levels. Here we report the identification of miR-125b-2 targets in the hematopoietic system by repressing miR125b in megakaryoblastic leukemia (AMKL) cell lines and overexpressing miR-125b-2 in hematopoietic stem and progenitor cells (CD34+-HSPCs)
Project description:In the previous studies, we reported that c-Mpl alternative splicing form c-Mpl-del overexpressed in acute megakaryoblasttic leukemia (AMKL) patients and mediated thrombopoietin signaling to promote AMKL cells malignant proliferation and chemotherapy resisitance. To investigate the detailed mechanism of c-Mpl-del mediated AMKL cells survival and chemotherapy resisitance, the AMKL cell Dami stably expressing GFP, c-Mpl-del-GFP or c-Mpl-p-GFP were established by transduction with GFP, c-Mpl-del-GFP or c-Mpl-p-GFP lentiviruses and treated with or without Ara-c (10μM) in the presence of 20ng/mL TPO for RNA-SEQ analysis to exame the expression of survival-related genes. Our results indicate that the levels of the "leading edge" genes that account for survival and prolieration are significantly higher in c-Mpl-del overexpressed AMKL cells. Meanwhile, the expression of c-Mpl-del promotes the tolerance of AMKL cells to Ara-c.
Project description:RATIONALE: Identification of genes that may be associated with developing certain types of cancer may someday provide important information about a person’s risk of getting cancer.
PURPOSE: This clinical trial is studying to see if certain genes may be associated with cancer in patients with cancer of the breast, prostate, lung, or colon and siblings of these patients.
Project description:Although high-risk human papillomavirus (HPV) infection plays a major role in the development of cervical cancer, additive oncogenic events are involved as well. One key event involves increased activity of telomerase resulting from a deregulated expression of its catalytic subunit hTERT. Our previous microcell-mediated chromosome transfer studies revealed that introduction of human chromosome 6 in the HPV16 immortalized keratinocyte cell line FK16A and in the HPV16 containing cervical cancer cell line SiHa induced growth arrest, resulting from a repression of hTERT mRNA expression and telomerase activity. Here, this model was used to analyze expression profiles associated with hTERT deregulation in HPV transformed cells. Microarray expression analysis of 12 FK16A/chromosome 6 hybrids, four of which were negative for endogenous hTERT and 8 of which were positive for endogenous hTERT, resulted in the identification of 164 differentially expressed genes. Differential expression of a selection of 5 genes was verified by real-time RT-PCR. Of these 164 genes, 32 were also differentially expressed in other HPV transformed cells with deregulated hTERT. For 2 of these genes, encoding AQP3 and MGP, altered expression in hTERT positive cervical carcinomas was confirmed by real-time RT-PCR and immunohistochemistry, respectively. In summary we identified 32 candidate biomarkers for deregulated hTERT mRNA expression which may enable the identification of cervical premalignant lesions that are at highest risk to progress to invasive cancer. Keywords: microarray expression analysis, hTERT, cervical cancer