Clinico-biological significance of suppressor of cytokine signaling 1 expression in acute myeloid leukemia
Journal
Blood cancer journal
Journal Volume
7
Journal Issue
7
Pages
e588
Date Issued
2017
Author(s)
Lu J.-W.
Lin T.-Y.
Liu C.-Y.
Tseng M.-H.
Chiang Y.-C.
Peng Y.-L.
Gong Z.
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.
SDGs
Other Subjects
SOCS1 protein, human; SOCS1 protein, zebrafish; suppressor of cytokine signaling 1; tumor marker; tumor protein; zebrafish protein; acute myeloid leukemia; adolescent; adult; aged; animal; biosynthesis; clinical trial; disease free survival; genetics; human; male; metabolism; middle aged; mortality; pathology; survival rate; transgenic animal; very elderly; zebra fish; Adolescent; Adult; Aged; Aged, 80 and over; Animals; Animals, Genetically Modified; Biomarkers, Tumor; Disease-Free Survival; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Neoplasm Proteins; Suppressor of Cytokine Signaling 1 Protein; Survival Rate; Zebrafish; Zebrafish Proteins
Type
journal article