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

N Hansen; H Ågerstam; M Wahlestedt; N Landberg; M Askmyr; M Ehinger; M Rissler; H Lilljebjörn; P Johnels; J Ishiko; J V Melo; W S Alexander; D Bryder; M Järås; T Fioretos

doi:10.1038/leu.2012.169

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

Leukemia. 2013 Jan;27(1):130-5. doi: 10.1038/leu.2012.169. Epub 2012 Jun 22.

Authors

N Hansen¹, H Ågerstam, M Wahlestedt, N Landberg, M Askmyr, M Ehinger, M Rissler, H Lilljebjörn, P Johnels, J Ishiko, J V Melo, W S Alexander, D Bryder, M Järås, T Fioretos

Affiliation

¹ Department of Clinical Genetics, University and Regional Laboratories, Lund University, Lund, Sweden.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Blotting, Western
Bone Marrow Cells / metabolism*
Disease Models, Animal*
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Fusion Proteins, bcr-abl / pharmacology*
Gene Expression Profiling
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells / metabolism*
Immunoenzyme Techniques
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / etiology*
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Oligonucleotide Array Sequence Analysis
Phosphorylation
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
STAT5 Transcription Factor / metabolism
Suppressor of Cytokine Signaling Proteins / physiology*
Survival Rate

Substances

Biomarkers, Tumor
RNA, Messenger
STAT5 Transcription Factor
Socs2 protein, mouse
Suppressor of Cytokine Signaling Proteins
Fusion Proteins, bcr-abl