Extensive Gene-Specific Translational Reprogramming in a Model of B Cell Differentiation and Abl-Dependent Transformation

Autor: Gregory J. Hogan, Patrick O. Brown, Damon May, Mark S. Schlissel, Jamie G. Bates, Patty B. Garcia, Martin W. McIntosh, Julia Salzman
Rok vydání: 2012
Předmět:
Proteomics
B Cells
Cellular differentiation
lcsh:Medicine
Gene Expression
Protein Synthesis
Biochemistry
Piperazines
Malignant transformation
Hematologic Cancers and Related Disorders
0302 clinical medicine
Bone Marrow
hemic and lymphatic diseases
Translational regulation
lcsh:Science
Oligonucleotide Array Sequence Analysis
Regulation of gene expression
B-Lymphocytes
0303 health sciences
Multidisciplinary
ABL
TOR Serine-Threonine Kinases
Cell Differentiation
Genomics
Acute Lymphoblastic Leukemia
3. Good health
Cell biology
Oncology
030220 oncology & carcinogenesis
Benzamides
Imatinib Mesylate
Medicine
Research Article
Oncogene Proteins v-abl
Immune Cells
Immunology
Chronic Myeloid Leukemia
Biology
Cell Line
Molecular Genetics
03 medical and health sciences
Leukemias
Genetics
Cancer Genetics
medicine
Humans
Gene Regulation
RNA
Messenger
030304 developmental biology
Sirolimus
Myeloproliferative Disorders
Precursor Cells
B-Lymphoid
lcsh:R
Proteins
Cancers and Neoplasms
Cell Transformation
Viral
medicine.disease
Molecular biology
Pyrimidines
Imatinib mesylate
Immune System
Polyribosomes
Protein Biosynthesis
lcsh:Q
Protein Translation
Genome Expression Analysis
Transcriptome
Protein Abundance
Chronic myelogenous leukemia
Zdroj: PLoS ONE
PLoS ONE, Vol 7, Iss 5, p e37108 (2012)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0037108
Popis: To what extent might the regulation of translation contribute to differentiation programs, or to the molecular pathogenesis of cancer? Pre-B cells transformed with the viral oncogene v-Abl are suspended in an immortalized, cycling state that mimics leukemias with a BCR-ABL1 translocation, such as Chronic Myelogenous Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL). Inhibition of the oncogenic Abl kinase with imatinib reverses transformation, allowing progression to the next stage of B cell development. We employed a genome-wide polysome profiling assay called Gradient Encoding to investigate the extent and potential contribution of translational regulation to transformation and differentiation in v-Abl-transformed pre-B cells. Over half of the significantly translationally regulated genes did not change significantly at the level of mRNA abundance, revealing biology that might have been missed by measuring changes in transcript abundance alone. We found extensive, gene-specific changes in translation affecting genes with known roles in B cell signaling and differentiation, cancerous transformation, and cytoskeletal reorganization potentially affecting adhesion. These results highlight a major role for gene-specific translational regulation in remodeling the gene expression program in differentiation and malignant transformation.
Databáze: OpenAIRE
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