PUBLICATION

Overexpression of SOX4 correlates with poor prognosis of acute myeloid leukemia and is leukemogenic in zebrafish

Authors
Lu, J.W., Hsieh, M.S., Hou, H.A., Chen, C.Y., Tien, H.F., Lin, L.I.
ID
ZDB-PUB-170827-8
Date
2017
Source
Blood cancer journal   7: e593 (Journal)
Registered Authors
Lin, Liang-In
Keywords
Cancer models, Risk factors
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Gene Expression Regulation, Neoplastic*
  • Leukemia, Myeloid, Acute/genetics
  • Leukemia, Myeloid, Acute/metabolism*
  • Leukemia, Myeloid, Acute/pathology
  • Myelopoiesis*
  • Neoplasm Proteins/biosynthesis*
  • Neoplasm Proteins/genetics
  • SOXC Transcription Factors/biosynthesis*
  • SOXC Transcription Factors/genetics
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/biosynthesis*
  • Zebrafish Proteins/genetics
PubMed
28841206 Full text @ Blood Cancer J
Abstract
The SOX4 transcription factor is a key regulator of embryonic development, cell-fate decision, cellular differentiation and oncogenesis. Abnormal expression of SOX4 is related to malignant tumor transformation and cancer metastasis. However, no reports are available regarding the clinical significance of SOX4 in acute myeloid leukemia (AML) and the role of SOX4 in leukemogenesis. In the current study, we found that AML patients with low bone marrow (BM) SOX4 expression had higher remission rates and longer overall survival than those with high SOX4 expression, regardless of age, white blood cell count at diagnosis, karyotype profile and NPM1/FLT3-ITD status. To elucidate the role of SOX4 in leukemogenesis, we generated a transgenic zebrafish model that overexpressed human SOX4 in the myeloid lineage Tg(spi1-SOX4-EGFP). These transgenic zebrafish showed, at 5 months of age, increased myelopoiesis with dedifferentiation in kidney marrow. At 9 months of age, their kidney structure was significantly effaced and distorted by increased infiltration of myeloid progenitor cells. These results suggest that SOX4 is not only an independent prognostic factor of AML, but also an important molecular factor in leukemogenesis.
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