title: SOCS2 is dispensable for BCR/ABL1-induced chronic myeloid leukemia-like disease and for normal hematopoietic stem cell function.
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.
authors: Department of Clinical Genetics, University and Regional Laboratories, Lund University, Lund, Sweden.
authors: N
authors: N
authors: Hansen
authors: H
authors: H
authors: Ågerstam
authors: M
authors: M
authors: Wahlestedt
authors: N
authors: N
authors: Landberg
authors: M
authors: M
authors: Askmyr
authors: M
authors: M
authors: Ehinger
authors: M
authors: M
authors: Rissler
authors: H
authors: H
authors: Lilljebjörn
authors: P
authors: P
authors: Johnels
authors: J
authors: J
authors: Ishiko
authors: J V
authors: JV
authors: Melo
authors: W S
authors: WS
authors: Alexander
authors: D
authors: D
authors: Bryder
authors: M
authors: M
authors: Järås
authors: T
authors: T
authors: Fioretos
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016044:Fusion Proteins, bcr-abl / Q000494:pharmacology*; D020869:Gene Expression Profiling; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins / Q000502:physiology*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; C491409:Socs2 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D016044:Fusion Proteins, bcr-abl