Prognostic Value of KMT2A and Downstream Gene Expression in AML Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
| Author | Sara Zehtabcheh | en |
| Author | Sahar Parkhideh | en |
| Author | Mahshid Mehdizadeh | en |
| Author | Mohammad Hossein Mohammadi | en |
| Author | Davood Bashash | en |
| Orcid | Sara Zehtabcheh [0009-0006-5998-1722] | en |
| Orcid | Sahar Parkhideh [0000-0001-7846-3222] | en |
| Orcid | Mahshid Mehdizadeh [0000-0002-8937-5495] | en |
| Orcid | Mohammad Hossein Mohammadi [0000-0002-8697-1371] | en |
| Orcid | Davood Bashash [0000-0002-8029-4920] | en |
| Issued Date | 2025-12-31 | en |
| Abstract | Background: Relapse following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a major cause of treatment failure in acute myeloid leukemia (AML). KMT2A, an epigenetic regulator, maintains hematopoietic homeostasis by modulating HOXA9, MEIS1, and PRDM16 — genes critical for leukemic stem cell (LSC) self-renewal. Objectives: The present study evaluated the expression of KMT2A and its downstream targets in AML patients post-allo-HSCT to assess their prognostic potential. Methods: Bone marrow (BM) samples from 42 participants (15 controls, 12 newly diagnosed AML, 15 post-HSCT AML) underwent RNA extraction, complementary DNA (cDNA) synthesis, and quantitative real-time PCR (qRT-PCR). Results: Significantly elevated expression of KMT2A and HOXA9 was observed in AML and HSCT-AML groups compared to controls (P < 0.0001). PRDM16 expression increased markedly only in de novo AML (P < 0.0001 vs. controls/HSCT-AML). MEIS1 showed no statistically significant differences across the groups; however, a non-significant increasing trend was observed in the de novo AML cohort. PRDM16 demonstrated exceptional diagnostic accuracy for AML (AUC = 0.966; sensitivity = 100%; specificity = 93.3%). Strong positive correlations existed between: KMT2A-PRDM16 (r = 0.818, P < 0.0001); KMT2A-HOXA9 (r = 0.680, P < 0.0001); HOXA9-PRDM16 (r = 0.699, P < 0.0001). Higher post-HSCT PRDM16 expression correlated with increased platelet counts (P = 0.019) and CD34+ cell doses (P = 0.032). Conclusions: PRDM16 is a highly sensitive and specific diagnostic biomarker for de novo AML. While KMT2A, HOXA9, and PRDM16 exhibit dysregulation in AML pathogenesis and post-HSCT, assessment of their expression at day +30 post-transplant did not predict early relapse. Integrating these genes into multi-parameter models or serial monitoring strategies may enhance prognostic utility. | en |
| DOI | https://doi.org/10.5812/ijcm-165616 | en |
| Keyword | Acute Myeloid Leukemia | en |
| Keyword | KMT2A | en |
| Keyword | HOXA9 | en |
| Keyword | MEIS1 | en |
| Keyword | PRDM16 | en |
| Keyword | Prognosis | en |
| Keyword | Relapse | en |
| Publisher | Brieflands | en |
| Title | Prognostic Value of KMT2A and Downstream Gene Expression in AML Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation | en |
| Type | Research Article | en |
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