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RNA-SEQ Quantitative Analysis of the regulation of c-Mpl-del on survival related gene transcriptome in AMKL cells

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE145949 | GEO | 2020/02/27

REPOSITORIES: GEO

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RNA-SEQ Quantitative Analysis of WT and Mpl-del-overexpressing AMKL cell Transcriptomes

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.

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RNA-SEQ Quantitative Analysis of the regulation of c-Mpl-del on survival related gene transcriptome in AMKL cells

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Gene therapy of Mpl -/- mouse LSK cells

Project description:Comparison of Mpl-/- mouse LSK cells, either treated with control (GFP) or Mpl lentivirus. Lineage negative bone marrow cells were isolated and transduced and transplanted into Mpl-/- recipient mice. After transplantation and follow up mice were sacrificed and LSK (lineage negative, Sca-1 positive, cKit positive) cells were isolated by FACS. RNA was isolated using RNeasy Micro Kit (Qiagen GmbH, Hilden, Germany) and RNA was amplified for microarray hybridization using the Nugen Ovation system (Nugen Technologies, AC Bemmel, Netherlands). The resulting material was hybridized to Affymetrix Mouse 430 2.0 arrays. RMA normalization and summarization was performed in R 2.10 using Bioconductor packages. The aim was to show the normalization of Mpl associated gene expression. 3 control (GFP transduced) samples of Mpl -/- mouse LSK cells and 3 treatment (Mpl transduced) samples of Mpl -/- mouse LSK cells.

2011-01-03 | E-GEOD-26403 | biostudies-arrayexpress

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Gene expression profiling of Down Syndrome (DS)-AMKL and non-DS AMKL samples

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.

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Gene expression changes induced by dimerization of intracellular c-Mpl in cord blood CD34+ progenitors

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Endocytosis of the thrombopoietin receptor Mpl regulates megakaryocyte and erythroid maturation in mice

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2022-08-25 | GSE206343 | GEO

Role of MPL expression in determining heterogeneity of leukemia-initiating capacity of chronic myelogenous leukemia stem cells

Project description:Using a CML mouse model, we identified differences in gene expression between leukemic compared with non-leukemic LTHSC, including increased expression of the thrombopoietin (THPO) receptor MPL. LTHSC expressing high levels of MPL showed enhanced JAK/STAT signaling and proliferation in response to THPO in vitro, and increased leukemogenic capacity in vivo compared to LTHSC with low MPL expression. Although both G0 and S-phase subpopulations were increased in MPL expressing LTHSC, LSC capacity was restricted to quiescent cells. Inhibition of MPL expression in CML LTHSC resulted in reduced THPO-induced JAK/STAT signaling and leukemogenic potential. Similar observations were made with LTHSC from CML patients. MPL expressing LTHSC demonstrated reduced sensitivity to BCR-ABL TKI treatment but demonstrated increased sensitivity to JAK inhibitors. Our studies identify MPL expression levels as a key determinant of heterogeneous leukemia-initiating capacity and drug sensitivity of CML LTHSC, and suggest that MPL-expressing CML stem cells are critical targets for therapy.

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