The HOTAIRM1-miR-222 Axis Regulates Venetoclax Resistance and Defines a High-Risk Subset in Pediatric t(8;21) Acute Myeloid Leukemia

Christine Wilson; Priyanka Swaroop; Vikas Gaur; Diwakar Sharma; Tanuja Bhardwaj; Sachin Kumar; Anita Chopra; Sampa Ghose; Jayanth Kumar Palanichamy; Deepam Pushpam; Ranjit Kumar Sahoo; Sameer Bakhshi; Surender Kumar Sharawat

doi:10.1101/2025.07.12.663834

Cancer BiologybioRxivJul 12, 2025

Preprint

The HOTAIRM1-miR-222 Axis Regulates Venetoclax Resistance and Defines a High-Risk Subset in Pediatric t(8;21) Acute Myeloid Leukemia

Christine Wilson iD, Priyanka Swaroop, Vikas Gaur iD, Diwakar Sharma iD, Tanuja Bhardwaj, Sachin Kumar iD, Anita Chopra iD, Sampa Ghose iD, Jayanth Kumar Palanichamy iD, Deepam Pushpam iD, Ranjit Kumar Sahoo iD, Sameer Bakhshi iD, Surender Kumar Sharawat iD

Abstract

Although acute myeloid leukemia (AML) with the RUNX1::RUNX1T1 fusion [t(8;21)(q22;q22.1)] defines a distinct cytogenetic subtype, differences in treatment response suggest additional molecular contributors beyond chromosomal abnormalities. Deregulated hematopoietic lineage-specific long non-coding RNAs (lncRNAs) contribute to leukemogenesis and therapy resistance. To investigate their role in t(8;21) AML, we performed whole-transcriptome sequencing of pediatric patients and age-matched healthy controls, identifying significant downregulation of lncRNA HOTAIRM1, a regulator of myeloid differentiation (adjusted P View larger version (53K): org.highwire.dtl.DTLVardef@19a0931org.highwire.dtl.DTLVardef@1d1a51aorg.highwire.dtl.DTLVardef@ae6783org.highwire.dtl.DTLVardef@de78e_HPS_FORMAT_FIGEXP M_FIG C_FIG

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