General AML

The clinical significance of SOX4 in AML – a Taiwan study

Sry-related High-mobility Group Box 4 (SOX4) is a transcription factor that plays a role in various developmental processes including embryonic development, cell-fate decision and cellular differentiation.1 The clinical implications of SOX4 expression in Acute Myeloid Leukemia (AML) is not yet elucidated.

Jeng-Wei Lu et al. from the National Taiwan University, Taipei, Taiwan, investigated the prognostic significance of SOX4 expression in the Bone Marrow (BM) of AML patients. The results of the study were reported in an article published in Blood Cancer Journal on 25th August 2017.2

BM samples from 112 de novo AML patients who were treated at National Taiwan University Hospital from March 2009 to December 2011 were analyzed for SOX4 expression using immunocytochemical staining. Based on the intensity and extent of BM SOX4 expression, patients were divided into two groups including low expression group (0–2, n = 62) and high expression group (3–4, n = 50).

The key results of the study were:
  • Patients with high SOX4 expression had increased relapse rates compared to patients with low SOX4 expression; 52.8% vs 26.5%, P = 0.028
  • Patients with low SOX4 expression had a significantly longer Overall Survival (OS [P = 0.008]) and Disease Free Survival (DFS [P = 0.013]) compared with patients with high SOX4 expression
  • High SOX4 expression was an independent poor prognostic factor for OS; Relative Risk = 1.924, P = 0.043

In summation, this study is the first to demonstrate that “increased BM SOX4 expression is an independent poor prognostic factor of OS in AML patients”.

Lu et al. concluded by proposing that BM SOX4 expression could serve as an “informative biomarker for the clinical prognosis of AML patients”. They further suggested that “agents that target SOX4 or its downstream molecules in addition to chemotherapy could be an effective strategy” for therapy in AML patients.

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.

References
  1. Liu F. et al. MicroRNA-138 attenuates epithelial-to-mesenchymal transition by targeting SOX4 in clear cell renal cell carcinoma. Am J Transl Res. 2017; 9(8): 3611–3622. Epub 2017 Aug 15.
  2. Lu J.W. et al. Overexpression of SOX4 correlates with poor prognosis of acute myeloid leukemia and is leukemogenic in zebrafish. Blood Cancer J. 2017 Aug 25; 7(8): e593. DOI: 10.1038/bcj.2017.74.