SOCS2 is dispensable for BCR/ABL1-induced chronic myeloid leukemia-like disease and for normal hematopoietic stem cell function.
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.
Department of Clinical Genetics, University and Regional Laboratories, Lund University, Lund, Sweden.
SourceLeukemia 27:1 2013 Jan pg 130-5
Bone Marrow Cells
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Fusion Proteins, bcr-abl
Gene Expression Profiling
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Mice, Inbred C57BL
Oligonucleotide Array Sequence Analysis
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
STAT5 Transcription Factor
Suppressor of Cytokine Signaling Proteins
Tumor Markers, Biological
Pub Type(s)Journal Article
Research Support, Non-U.S. Gov't