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

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 significan...

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Bibliographic Details
Published in:Blood cancer journal (New York) 2017-08, Vol.7 (8), p.e593-e593
Main Authors: Lu, J-W, Hsieh, M-S, Hou, H-A, Chen, C-Y, Tien, H-F, Lin, L-I
Format: Article
Language:English
Subjects:
Animals
Animals, Genetically Modified
Gene Expression Regulation, Neoplastic
Leukemia
Leukemia, Myeloid, Acute - genetics
Leukemia, Myeloid, Acute - metabolism
Leukemia, Myeloid, Acute - pathology
Medical prognosis
Myelopoiesis
Neoplasm Proteins - biosynthesis
Neoplasm Proteins - genetics
Original
SOXC Transcription Factors - biosynthesis
SOXC Transcription Factors - genetics
Zebrafish - genetics
Zebrafish - metabolism
Zebrafish Proteins - biosynthesis
Zebrafish Proteins - genetics
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Summary: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.
ISSN:2044-5385
2044-5385
DOI:10.1038/bcj.2017.74