SOX gene expression in adult de novo AML

SOX (SRY-related high mobility group [HMG] box) genes encode a family of transcription factors, which play an important role in regulation of cell fate differentiation and specification during development. The role of SOX gene family in leukemia pathogenesis and its clinical significance has not been evaluated yet. Natasa Tosic from the University of Belgrade, Belgrade, Serbia, and colleagues, examined the association between expression levels and  prognostic significance of SOX genes in Acute Myeloid Leukemia (AML). The results were published in Leukemia Research.

Using RQ-PCR, Tosic et al. specifically examined the expression profiles of SOX2, SOX3, SOX11, SOX14 and SOX18 genes in Bone Marrow (BM) samples of 50 newly diagnosed adult de novo AML patients and 12 healthy controls. Of all the genes examined, SOX2 gene expression level was significantly different between AML patients and healthy controls. Using a cut-off value, patients were divided into low and high SOX gene expression groups.  

Key findings:

• SOX2 expression

  • Using a cut-off value of 3.39, 10% (5/50) of patients had high SOX2 (SOX2high) expression
  • SOX2high status associated significantly with mutations in NPM1 (P = 0.018) and IDH2 (P = 0.021)
  • Compared to patients with low SOX2 gene expression, Disease Free Survival (DFS) and Overall Survival (OS) were significantly shorter in patients with SOX2high status

• SOX3 expression

  • Using a cut-off value of 3.60, 22% (11/50) of patients had high SOX3 (SOX3high) expression
  • Compared to patients with low SOX3 expression, DFS and OS was shorter in patients with SOX3high status

• SOX11 expression

  • Using a cut off value of 2.84, 16% (8/50) of patients had higher levels of SOX11 (SOX11high) expression
  • SOX11high status was associated significantly with FLT3/ITD (P = 0.001) and NPM1 (P = 0.021) mutations
  • DFS in patients with SOX11high status was significantly shorter than patients with low SOX11 expression, P < 0.001

• SOX14 expression

  • At a cut-off value of 2.86, 20% (10/50) of patients had high level of SOX14 (SOX14high) expression
  • SOX14high status associated significantly with FLT3/ITD mutations, P = 0.006
  • Patients with SOX14high status had shorter DFS compared to patients with low SOX14 levels, P = 0.001

• SOX18 expression

  • With the implementation of cut-off value (5.57), 18% (9/50) of patients had high SOX18 (SOX18high) expression
  • NPM1 and FLT3/ITD mutations were correlated with SOX18high status, P = 0.003 and P = 0.002, respectively
  • Compared to patients with low SOX18 expression, DFS (P = 0.001) and OS (P = 0.046) were significantly shorter in patients with SOX18high status

In summary, this is the first study to examine the expression levels of SOX2, SOX3, SOX11, SOX14 and SOX18 in adult patients with de novo AML. The authors concluded by noting that the preliminary findings of their study “indicates that overexpression of SOX genes might have negative prognostic implications” on the pathogenesis of AML.

The authors further added that even if this study had its limitations due to small sample size, based on the initial findings, further trials investigating these genes and their role in pathogenesis as well as prognosis in AML patients are required.