Editorial: Special issue on innovative multi-disciplinary approaches for precision studies in leukemia

Marmiroli, S., Huang, X. , Serafin, V. and Michie, A. M. (2021) Editorial: Special issue on innovative multi-disciplinary approaches for precision studies in leukemia. Frontiers in Oncology, 11, 744009. (doi: 10.3389/fonc.2021.744009)

Abstract

Dissection of the heterogeneous and complex biological mechanisms of leukemia, elucidating the role of recurrent mutations and epigenetic modifications as well as aberrant activation of oncogenic signaling (1)(2)(3)(4), have advanced our understanding of leukemogenesis allowing precision medicine to transform approaches to diagnosis and therapy. In this Research Topic we focused on innovative technologies that will aid in the development of a multi-dimensional integrated molecular network, enabling the prediction of therapy responses and create novel treatments for those of most clinical need. We were delighted to receive ten exciting contributions, featuring a comprehensive update of the current potential and limitations of preclinical and clinical advancements.Risk stratification scores in AML are important tools for clinicians and scientists alike, due to the relative ease with which biomarker panels can assist with diagnosis, prediction of prognosis, overall survival (OS) and guide appropriate treatment choices. Our work has identified a gene signature associated with the histone demethylase KDM4A, the KDM4A-9 score, which is associated with poor OS and independent of age, cytogenetic risk and mutation status (2). KDM4A-9 is highly correlative with the LSC17 score, while having no overlap, showing the collective power of integrating risk scoring systems (2,5). In this Special Issue, Unlike most reviews on the same subject, it focused also on AML "persisters" highlighting that they are not necessarily pre-existing but arise by distinct mechanisms and may be induced by therapy. Understanding the plasticity of these mechanisms in different patients could lead to effective personalized therapy.Metabolic reprogramming is a key hallmark of cancer and gaining a fundamental understanding of disease biology in terms of metabolic profiling may enable personalized therapies that exploit the unique weaknesses in leukemic cells. As such, Zhang et al. analyzed publicly-available databases to investigate metabolism-related prognostic factors and identified four genes (PLA2G4A, HMOX2, AK1, SMPD3) that when highly expressed represented a poor prognostic predictor for AML patients. Dembitz and Gallipoli described recent evidence demonstrating the validity of developing therapies that target metabolic pathways in AML. The review highlights the differential metabolic pathways that are present in distinct AML subtypes and disease stages, which may enable truly personalized treatments for these patients, supported by FDA approval of the first metabolic inhibitors targeting IDH1/2 in AML. Further promising avenues for targeting metabolic pathways are discussed.The impact that the microenvironmental niche has on tumor persistence is now becoming Hematopoietic stem cell transplantation (SCT) represents a potential cure for acute leukemia, however as most hematological malignancies occur in older individuals, in which the myeloablative conditioning regimen prior to SCT is linked to a high risk of treatment-related mortality (TRM), this is not always possible. Incorporating reduced intensity conditioning (low dose fludarabine and cyclophosphamide) in patients with acute leukemia/MDS of ≥55 years old revealed that OS, leukemia free survival, TRM, and cumulative incidence of relapse were comparable to a historical, younger cohort of patients that underwent the normal conditioning regimen. This small study suggests that a reduction in the conditioning regimen prior to SCT may be a feasible option for older acute leukemia patients.In summary, although treatment of leukemia remains a challenge, by highlighting new research avenues, therapeutic targets and strategies, the articles in this Issue will inform scientists and clinicians, expanding the potential for development of non-canonical diagnostics or interventions.

• Item Type: Articles
• Additional Information: Funding: SM: A.MA.RI.CA. E95F21001040007, AM: Blood Cancer UK project grant Ref. 18003, VS: AIRC MFAG 2018 ID 21771.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Michie, Professor Alison and Huang, Dr Xu
• Authors: Marmiroli, S., Huang, X., Serafin, V., and Michie, A. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Frontiers in Oncology
• Publisher: Frontiers Media
• ISSN: 2234-943X
• ISSN (Online): 2234-943X
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Frontiers in Oncology 11:744009
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
303091		Elucidating the mechanisms that regulate FOXO activity in chronic lymphocytic leukaemia - a novel target for therapeutic exploitation?	Alison Michie	Bloodwise (BLOODWIS)	18003	CS - Paul O'Gorman Leukaemia Research Centre