SOCS2 is dispensable for BCR/ABL1-induced chronic myeloid leukemia-like disease and for normal hematopoietic stem cell function

Autor: Henrik Lilljebjörn, David Bryder, Nils Hansen, Junia V. Melo, Marcus Järås, Martin Wahlestedt, Thoas Fioretos, Petra Johnels, Niklas Landberg, Warren S. Alexander, Marianne Rissler, Maria Askmyr, Jun Ishiko, Helena Ågerstam, Mats Ehinger
Rok vydání: 2012
Předmět:
Male
Cancer Research
medicine.medical_treatment
Fusion Proteins
bcr-abl
Suppressor of Cytokine Signaling Proteins
Hematopoietic stem cell transplantation
HSC
BCR/ABL1
Immunoenzyme Techniques
Mice
hemic and lymphatic diseases
STAT5 Transcription Factor
SOCS2
Phosphorylation
CML
Oligonucleotide Array Sequence Analysis
Mice
Knockout
ABL
Reverse Transcriptase Polymerase Chain Reaction
Hematopoietic Stem Cell Transplantation
breakpoint cluster region
Hematopoietic stem cell
Myeloid leukemia
Hematology
Flow Cytometry
Survival Rate
Leukemia
medicine.anatomical_structure
Oncology
Original Article
Female
Blotting
Western
Bone Marrow Cells
Enzyme-Linked Immunosorbent Assay
Biology
Real-Time Polymerase Chain Reaction
Leukemia
Myelogenous
Chronic
BCR-ABL Positive
STAT5 phosphorylation
Biomarkers
Tumor
medicine
Animals
RNA
Messenger
Gene Expression Profiling
Hematopoietic Stem Cells
medicine.disease
Mice
Inbred C57BL
Transplantation
Disease Models
Animal
Cancer and Oncology
Cancer research
Zdroj: Leukemia
Leukemia; 27, pp 130-135 (2013)
ISSN: 1476-5551
0887-6924
DOI: 10.1038/leu.2012.169
Popis: Suppressor of cytokine signaling 2 (SOCS2) is known as a feedback inhibitor of cytokine signaling and is highly expressed in primary bone marrow (BM) cells from patients with chronic myeloid leukemia (CML). However, it has not been established whether SOCS2 is involved in CML, caused by the BCR/ABL1 fusion gene, or important for normal hematopoietic stem cell (HSC) function. In this study, we demonstrate that although Socs2 was found to be preferentially expressed in long-term HSCs, Socs2-deficient HSCs were indistinguishable from wild-type HSCs when challenged in competitive BM transplantation experiments. Furthermore, by using a retroviral BCR/ABL1-induced mouse model of CML, we demonstrate that SOCS2 is dispensable for the induction and propagation of the disease, suggesting that the SOCS2-mediated feedback regulation of the JAK/STAT pathway is deficient in BCR/ABL1-induced CML.Leukemia advance online publication, 24 July 2012; doi:10.1038/leu.2012.169.
Databáze: OpenAIRE
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