Prognostic impact of PRDM16 expression in acute myeloid leukemia with normal cytogenetics

ABSTRACT

Purpose

Cytogenetically normal acute myeloid leukemia (CN-AML) is a heterogeneous disease with variable clinical outcomes. The identification of potential biomarkers to better classify the patients with unfavorable prognoses who may require more aggressive therapies is an emergent demand. PRDM16 is a transcriptional cofactor and histone methyltransferase, playing a critical role in maintaining hematopoietic stem cells, and MLL fusion-induced leukemogenesis. However, the prognostic value of PRDM16 in CN-AML is still unclear.

Materials and Methods

We retrospectively analyzed the PRDM16 expression and its association with gene mutations in CN-AML. Then the prognostic value of PRDM16 and its comparison with WT1 were analyzed.

Results

The results showed that about 73.6% of CN-AML patients harbored higher expression of PRDM16 than the healthy controls. Furthermore, CN-AML patients with high PRDM16 expression had a lower survival rate than the low PRDM16 expression group (50.5% vs. 83.3%, p = 0.0339). Interestingly, hemopoietic stem cell transplantation significantly improved the prognosis of CN-AML with high PRDM16 expression but not those with low PRDM16 expression. In terms of molecular genetics, high PRDM16 expression was significantly associated with a lower rate of CEBPA mutation (p = 0.01) and a higher rate of FLT3-ITD and DNMT3A mutation (p = 0.032 and p = 0.004, respectively). In addition, PRDM16 expression was significantly correlated with WT1 expression in CN-AML (r = 0.7, p < 0.001). These data suggested PRDM16 expression could be used to predict the outcome of patients with CN-AML.

Conclusion

PRDM16 is significantly associated with FLT3-ITD and DNMT3A mutation and WT1 expression and serves as a potential prognostic biomarker in CN-AML.

KEYWORDS:

• PRDM16
• CN-AML
• prognosis
• WT1
• FLT3-ITD

Acknowledgements

All the samples were from Hematological Biobank, Jiangsu Biobank of Clinical Resources.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Nature Science Foundation of Jiangsu Province [grant number BE2018652] and The Natural Science Foundation of the Jiangsu Higher Education Institutions of China [grant number 21KJD320002].