The original paper, published on 23 May 2019 by a team of researchers at the University of Bologna and the Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori in Meldola, reported that hyper-activation of a signaling axis involving Aurora kinase A, polo-like kinase 1, and the transcription factor FOXM1 promotes resistance to tyrosine kinase inhibitors in chronic myeloid leukemia. The work attracted attention because it pointed to a route of drug escape that operates independently of the BCR-ABL fusion protein, the canonical target of imatinib and its successor drugs. Resistance that arises through BCR-ABL mutations can often be tackled with second- and third-generation inhibitors, but resistance driven by downstream survival pathways is a thornier clinical problem.

To understand why the finding mattered, it helps to unpack the molecular machinery involved. Aurora kinase A is a serine-threonine kinase best known for its role in mitosis, where it orchestrates centrosome maturation, spindle assembly, and entry into mitosis through activation at threonine 288, a key autophosphorylation site. Polo-like kinase 1, or PLK1, is another mitotic kinase that acts downstream and in parallel, coordinating checkpoint recovery and cytokinesis, with its own activating phosphorylation at threonine 210. FOXM1 is a proliferation-associated transcription factor that drives the expression of genes required for cell-cycle progression, and it is a well-documented transcriptional target of PLK1 signaling. Together, these three components form a coherent mitotic regulatory cascade, and overactivity of such cascades is a hallmark of many cancers, including leukemias.

The Bologna group’s central claim was that in chronic myeloid leukemia, this axis can become hyper-activated in a way that sustains leukemic cell survival even when BCR-ABL kinase activity is pharmacologically silenced. In practical terms, the suggestion was that imatinib, dasatinib, nilotinib, and related drugs might fail in some patients not because the target enzyme mutates, but because the leukemia cells acquire or amplify an alternative pro-survival program centered on mitotic kinase signaling. If true, the implication for therapy would be significant: combining tyrosine kinase inhibitors with Aurora kinase A or PLK1 inhibitors could potentially resensitize resistant cells, offering a rational combination strategy for patients whose disease no longer responds to standard treatment.

Chronic myeloid leukemia is, in many respects, the great success story of targeted cancer therapy. The Philadelphia chromosome, the characteristic translocation that generates the BCR-ABL fusion kinase, provided a single, druggable driver, and imatinib’s approval in 2001 converted a uniformly fatal disease into a manageable chronic condition for most patients. Yet a stubborn minority of patients fail therapy, and the mechanisms of failure fall into two broad categories. The first is BCR-ABL-dependent resistance, typically caused by point mutations in the kinase domain, including the notoriously difficult T315I mutation. The second is BCR-ABL-independent resistance, in which leukemic stem cells or progenitors survive through alternative signaling routes, efflux pumps, quiescence, or epigenetic adaptations. The Aurora A-PLK1-FOXM1 hypothesis belongs squarely in this second category, which is precisely why it generated interest among translational researchers.

The expression of concern, published on 12 October 2026 as volume 45, article number 214 of the journal, does not invalidate the paper’s hypothesis outright, but it casts doubt on a specific body of supporting evidence. According to the notice, concerns were raised regarding highly similar images in the article. Specifically, the Editor-in-Chief flagged that Figure 1C and Figure 1E show similar band appearances in corresponding lanes, particularly for the phosphorylated forms of Aurora kinase A at threonine 288 and PLK1 at threonine 210. These two western blot signals are central to the paper’s argument, because they represent the experimental readout of the pathway’s activation state. If the bands cannot be trusted, the evidence that the axis is hyper-activated in resistant cells is weakened at its foundation.

The journal’s handling of the matter followed established post-publication correction procedures. The authors were asked to respond and, according to the notice, provided raw data upon request. However, the raw image files could not be conclusively verified, leaving the concerns unresolved. In such situations, editors typically face a choice between a full retraction, which asserts that the findings are unreliable, and an expression of concern, which is an interim or standing alert telling readers to interpret specific data with caution. The Editor-in-Chief chose the latter, advising readers to treat the affected figures with care while stopping short of retracting the entire article. This calibrated response reflects the reality that image duplication does not necessarily indicate misconduct, and that some concerns can never be definitively adjudicated when original files are unavailable or ambiguous.

Equally revealing is the split among the author group itself. According to the published notice, M. Mancini, S. De Santis, C. Monaldi, F. Castagnetti, G. Gugliotta, G. Rosti, and S. Soverini disagree with the editorial expression of concern, while L. Bavaro, M. Martelli, M. A. Santucci, G. Martinelli, and M. Cavo did not respond to correspondence from the publisher. This divergence within a single research team is uncommon in public notices and underscores how contested such judgments can be. Authors who disagree may believe the raw data, even if not conclusively verifiable, still support the conclusions, or that the flagged similarities reflect technical artifacts of western blotting rather than duplication. Western blot images are notoriously prone to interpretation disputes, since band patterns can appear similar across lanes for reasons ranging from sample loading characteristics to scanning and assembly of figure panels.

For the wider leukemia research community, the notice is a reminder of how the field’s understanding of tyrosine kinase inhibitor resistance continues to evolve. The BCR-ABL-independent resistance literature includes contributions from many laboratories, and the Aurora A-PLK1-FOXM1 axis remains one of several proposed mechanisms, alongside alterations in stromal niche signaling, drug efflux transporters, and stem cell quiescence programs. Any single study’s evidentiary problems do not erase the broader biological plausibility of mitotic kinase involvement in drug-tolerant leukemic cells, but they do mean that researchers citing the 2019 paper must now do so with explicit caution. Databases and indexing services link the expression of concern to the original article, which was published under DOI 10.1186/s13046-019-1197-9, while the notice itself carries the DOI 10.1186/s13046-026-03848-7.

The episode also illustrates the changing economics of scientific trust. Open-access publishing, under which this journal operates with a Creative Commons Attribution 4.0 license, maximizes the dissemination of findings, but it also depends on robust post-publication oversight to maintain credibility. Tools such as CrossMark, which flags updated versions of records, and the growing use of image-integrity screening mean that papers published years ago can still face scrutiny today. For patients and clinicians, the practical takeaway is unchanged: tyrosine kinase inhibitors remain the cornerstone of chronic myeloid leukemia care, and resistance management continues to rely on mutation monitoring and sequential inhibitor switching. For scientists, the message is sharper. A striking hypothesis about how leukemia cells outsmart targeted drugs now stands on contested evidence, and the burden of verification rests with those who would build on it. The expression of concern will remain attached to the record unless the underlying concerns are resolved, a resolution that, on current evidence, neither the journal nor the divided author group can yet deliver.

Subject of Research: Editorial expression of concern regarding a study of Aurora kinase A–PLK1–FOXM1 axis-mediated tyrosine kinase inhibitor resistance in chronic myeloid leukemia

Article Title: Editorial expression of concern: Hyper-activation of Aurora kinase a-pololike kinase 1-FOXM1 axis promotes chronic myeloid leukemia resistance to tyrosine kinase inhibitors

Article References: Mancini, M., De Santis, S., Monaldi, C., Bavaro, L., Martelli, M., Castagnetti, F., Gugliotta, G., Rosti, G., Santucci, M. A., Martinelli, G., Cavo, M., & Soverini, S. (2026). Editorial expression of concern: Hyper-activation of Aurora kinase a-pololike kinase 1-FOXM1 axis promotes chronic myeloid leukemia resistance to tyrosine kinase inhibitors. Journal of Experimental & Clinical Cancer Research, 45(1), Article 214. https://doi.org/10.1186/s13046-026-03848-7

Image Credits: AI Generated

DOI: 10.1186/s13046-026-03848-7

Keywords: chronic myeloid leukemia, Aurora kinase A, polo-like kinase 1, FOXM1, tyrosine kinase inhibitors, drug resistance, editorial expression of concern, image integrity, BCR-ABL, post-publication scrutiny, western blot, Journal of Experimental & Clinical Cancer Research