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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Pediatric Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1445173
This article is part of the Research Topic Pediatric Myeloid Neoplasms: New Insights Into Diagnosis, Prognosis, and Treatment View all articles

ARMH1 is a novel marker associated with poor pediatric AML outcomes that affect the fatty acid synthesis and cell cycle pathways.

Provisionally accepted
Mojtaba Bakhtiari Mojtaba Bakhtiari 1,2Sean Jordan Sean Jordan 1Hope L. Mumme Hope L. Mumme 1Richa Sharma Richa Sharma 1Mala Shanmugam Mala Shanmugam 1,3Swati Bhasin Swati Bhasin 1,2Manoj Bhasin Manoj Bhasin 1,2*
  • 1 Emory University, Atlanta, United States
  • 2 Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Atlanta, Colorado, United States
  • 3 Winship Cancer Institute, Emory University, Atlanta, Georgia, United States

The final, formatted version of the article will be published soon.

    Despite remarkable progress in Pediatric Acute Myeloid Leukemia (pAML) treatments, the relapsed disease remains difficult to treat, making it pertinent to identify novel biomarkers of prognostic/therapeutic significance. Our data shows that ARMH1, a novel cancer-associated gene is highly expressed in the malignant blast cells of multiple pediatric hematologic malignancies including AML, T/B-ALL, and T/B-MPAL. Notably, ARMH1 expression is significantly elevated in blast cells of patients who relapsed or have a high-risk cytogenetic profile (MLL) compared to standard-risk (RUNX1, inv ( 16)). ARMH1 expression is also significantly correlated with the pediatric leukemia stem cell score of 6 genes (LSC6) associated with poor outcomes. Perturbation of ARMH1 (knockdown and overexpression) in leukemia cell lines significantly impacted cell proliferation and migration. The RNA-sequencing analysis on multiple ARMH1 knockdown and overexpressing cell lines established an association with mitochondrial fatty acid synthesis and cell cycle pathways. The investigation of the mitochondrial matrix shows that pharmacological inhibition of a key enzyme in fatty acid synthesis regulation, CPT1A, resulted in ARMH1 downregulation. ARMH1 knockdown also led to a significant reduction in CPT1A and ATP production as well as Oxygen Consumption Rate. Our data indicates that downregulating ARMH1 impacts cell proliferation by reducing key cell cycle regulators such as CDCA7 and EZH2. Further, we also established that ARMH1 is a key physical interactant of EZH2, associated with multiple cancers. Our findings underscore further evaluation of ARMH1 as a potential candidate for targeted therapies and the stratification of aggressive pAML to improve outcomes.

    Keywords: AML, Cell Cycle, Fatty acid metabolic pathway, EZH 2, CDCA7

    Received: 06 Jun 2024; Accepted: 04 Nov 2024.

    Copyright: © 2024 Bakhtiari, Jordan, Mumme, Sharma, Shanmugam, Bhasin and Bhasin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Manoj Bhasin, Emory University, Atlanta, United States

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