Anticancer research · 2025
HOX-PBX Up-regulation Predicts Favorable Prognosis in NPM1-mutated Normal Cytogenetic AML via WNT Signaling.
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Elyamany Ghaleb, Alotaibi Sultan, Alharbi Bander, Alhafi Osama Atallah, Aljasem Hassan, Jamil Hadi, Roshan Tariq M, Akhter Ariz, Mansoor Adnan
Аннотация
BACKGROUND/AIM: Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy. HOX gene dysregulation, particularly within the HOXA cluster, plays a critical role in leukemogenesis. This study investigated the impact of HOX-PBX gene expression and its association with clinical outcomes in NPM1-mutated cytogenetically normal (CN)-AML.
MATERIALS AND METHODS: Gene expression analysis was performed on diagnostic bone marrow samples from 35 CN-AML patients using the NanoString nCounter platform. Differential expression of HOXA9, HOXA10, and PBX3 was assessed, along with correlations with NPM1 mutation status and WNT pathway activation. Kaplan-Meier survival analysis was conducted to evaluate prognostic significance.
RESULTS: HOXA9 and HOXA10 were significantly up-regulated in NPM1-mutated AML compared to NPM1-negative cases (p<0.001). PBX3 expression strongly correlated with HOXA10 (r=0.86, p<0.001), suggesting a cooperative role in leukemogenesis. Elevated HOXA9 (>589.7) was associated with improved survival (hazard ratio=0.3, p=0.021). Up-regulated WNT pathway targets (MYC, RUNX1) in NPM1-mutated cases indicate active WNT/β-catenin signaling, potentially promoting differentiation and favorable prognosis.
CONCLUSION: HOX-PBX-WNT interactions contribute to the distinct biology of NPM1-mutated CN-AML. Targeting this axis may offer novel therapeutic strategies for AML, warranting further research into molecular-driven treatments for AML.
MATERIALS AND METHODS: Gene expression analysis was performed on diagnostic bone marrow samples from 35 CN-AML patients using the NanoString nCounter platform. Differential expression of HOXA9, HOXA10, and PBX3 was assessed, along with correlations with NPM1 mutation status and WNT pathway activation. Kaplan-Meier survival analysis was conducted to evaluate prognostic significance.
RESULTS: HOXA9 and HOXA10 were significantly up-regulated in NPM1-mutated AML compared to NPM1-negative cases (p<0.001). PBX3 expression strongly correlated with HOXA10 (r=0.86, p<0.001), suggesting a cooperative role in leukemogenesis. Elevated HOXA9 (>589.7) was associated with improved survival (hazard ratio=0.3, p=0.021). Up-regulated WNT pathway targets (MYC, RUNX1) in NPM1-mutated cases indicate active WNT/β-catenin signaling, potentially promoting differentiation and favorable prognosis.
CONCLUSION: HOX-PBX-WNT interactions contribute to the distinct biology of NPM1-mutated CN-AML. Targeting this axis may offer novel therapeutic strategies for AML, warranting further research into molecular-driven treatments for AML.