PUBLICATION

Clinico-biological significance of suppressor of cytokine signaling 1 expression in acute myeloid leukemia

Authors
Hou, H.A., Lu, J.W., Lin, T.Y., Tsai, C.H., Chou, W.C., Lin, C.C., Kuo, Y.Y., Liu, C.Y., Tseng, M.H., Chiang, Y.C., Peng, Y.L., Tang, J.L., Gong, Z., Lin, L.I., Tien, H.F.
ID
ZDB-PUB-170729-2
Date
2017
Source
Blood cancer journal   7: e588 (Journal)
Registered Authors
Gong, Zhiyuan, Lin, Liang-In, Lin, Tzung-Yi
Keywords
Cancer genetics, Oncogenes
MeSH Terms
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Animals, Genetically Modified
  • Biomarkers, Tumor/biosynthesis*
  • Biomarkers, Tumor/genetics
  • Disease-Free Survival
  • Humans
  • Leukemia, Myeloid, Acute/genetics
  • Leukemia, Myeloid, Acute/metabolism*
  • Leukemia, Myeloid, Acute/mortality*
  • Leukemia, Myeloid, Acute/pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins/biosynthesis*
  • Neoplasm Proteins/genetics
  • Suppressor of Cytokine Signaling 1 Protein/biosynthesis*
  • Suppressor of Cytokine Signaling 1 Protein/genetics
  • Survival Rate
  • Zebrafish
  • Zebrafish Proteins/biosynthesis
  • Zebrafish Proteins/genetics
PubMed
28753595 Full text @ Blood Cancer J
Abstract
Suppressor of cytokine signaling 1 (SOCS1) protein, which encodes a member of signal transducers and activators of transcription-induced inhibitors, takes part in a negative regulation of cytokine signaling. The mechanism of SOCS1 in tumor carcinogenesis is complex and there have been no studies concerning the clinic-biologic implication of SOCS1 expression in acute myeloid leukemia (AML). Here, we first identified that higher bone marrow (BM) SOCS1 expression was closely associated with older age, FLT3-ITD, NPM1 and DNMT3A mutations, but negatively correlated with CEBPA mutation in patients with de novo AML. Compared to patients with lower SOCS1 expression, those with higher expression had lower complete remission rates and shorter overall survival. Further, higher expression of SOCS1 in the BM was an independent unfavorable prognostic factor irrespective of age, white blood cell, cytogenetics and gene mutations. Next, we generated zebrafish model overexpressing SOCS1 by spi1 promoter, which showed kidney marrow from adult SOCS1 zebrafish had increased myelopoiesis, myeloid progenitors and the kidney or spleen structure were effaced and distorted, mimicking leukemia phenotype. The SOCS1/FLT3-ITD double transgenic fish could further facilitate the leukemic process. The results indicate SOCS1 plays an important role in AML and its higher expression serves as a new biomarker to risk-stratify AML patients.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes