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DDIT4: Prognostic Marker and Therapeutic Target in AML

April, 04, 2024 | AML (Acute Myeloid Leukemia), Leukemia

KEY TAKEAWAYS

  • The study aimed to investigate the prognostic value and functional role of DDIT4 in AML patients.
  • Researchers noticed that DDIT4 shows promise as both a prognostic marker and a possible therapeutic target for AML patients.

Acute myeloid leukemia (AML) is a hematological malignancy characterized by abnormal proliferation of immature leukocytes in the hematopoietic system. Despite its known involvement in tumorigenesis, the role of DNA-damage-inducible transcript 4 (DDIT4) in AML remains poorly understood. DDIT4, known as a negative regulator of the rapamycin inhibitor, participates in various cellular functions.

Fangmei Li and his team aimed to understand the role of DDIT4 in AML, concentrating on its prognostic value and potential therapeutic implications.

Researchers performed an inclusive analysis, examining the expression of DDIT4 in AML patients through The Cancer Genome Atlas data and real-time polymerase chain reaction. The Chi-square test assessed the correlation between DDIT4 expression and clinical characteristics in AML patients.

Loss-of-function experiments were conducted to investigate DDIT4’s role in AML carcinogenesis. The R package was also utilized to evaluate the correlation between DDIT4 expression and immune cell populations.

The results demonstrated that the expression of DDIT4 is significantly associated with Age, Cytogenetic risk, Cytogenetics, and overall survival (OS) events among AML patients. Notably, elevated DDIT4 expression correlates with poorer prognosis.

KEGG analysis revealed the involvement of differently expressed genes (DEGs) in the PI3-Akt signaling pathway, while GSEA enrichment analysis indicated DEGs’ correlation with apoptosis. Functional experiments highlighted DDIT4 knockdown inhibited cell cycle transition/proliferation and promoted apoptosis. Furthermore, DDIT4 was found to be associated with immune infiltration.

The study concluded that DDIT4 serves as a validated prognostic marker and holds promise as a potential therapeutic target for AML.

The study was sponsored by the Natural Science Foundation of Shaanxi Province.

Source: https://pubmed.ncbi.nlm.nih.gov/38507057/

Li F, Miao J, Liu R, et al. (2024). “Pan-cancer analysis of DDIT4 identifying its prognostic value and function in acute myeloid leukemia.” J Cancer Res Clin Oncol. 2024 Mar 20;150(3):144. doi: 10.1007/s00432-024-05676-8. PMID: 38507057; PMCID: PMC10954950.

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