Evidence map›Paper›PMID 42649960›Full record

ReviewCancers2026

Functional Characterization of Myelodysplastic Syndrome by Multiparameter Flow Cytometry: The Clinical Synergy Between Ki-67 and Bcl-2 and Their Potential Role in Diagnostics and Personalized Therapy.

Sixuan J Wang, Rinaldo A J N van Meel, Stefan G C Mestrum, Thomas H P M Habets, Anton H N Hopman, Frans C S Ramaekers, Yvonne M C Henskens, Otto Bekers, Mathie P G Leers

Abstract readReview
In one paragraph

Review in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Sixuan J WangDepartment of Clinical Chemistry & Hematology, Zuyderland Medical Center, 6162 BG Sittard-Geleen, The Netherlands.
Rinaldo A J N van MeelDepartment of Clinical Chemistry & Hematology, Zuyderland Medical Center, 6162 BG Sittard-Geleen, The Netherlands.ORCID 0009-0003-2440-4640
Stefan G C MestrumDepartment of Clinical Chemistry & Hematology, Zuyderland Medical Center, 6162 BG Sittard-Geleen, The Netherlands.
Thomas H P M HabetsDepartment of Radiation Oncology (Maastro), GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands.
Anton H N HopmanDepartment of Genetics & Cell Biology, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands.
Frans C S RamaekersDepartment of Genetics & Cell Biology, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands.
Yvonne M C HenskensCentral Diagnostic Laboratory (CDL), Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands.
Otto BekersCentral Diagnostic Laboratory (CDL), Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands.ORCID 0000-0003-2902-2927
Mathie P G LeersDepartment of Clinical Chemistry & Hematology, Zuyderland Medical Center, 6162 BG Sittard-Geleen, The Netherlands.ORCID 0000-0001-5186-5600

Funding

Research and Innovation Foundation of Zuyderland MC
6 · The paper itself

Abstract

The diagnosis and clinical management of myelodysplastic neoplasms are increasingly challenged by the disease's inherent heterogeneity, particularly with respect to the diagnosis of low-grade variants. While standardized flow cytometric protocols traditionally rely on static biomarkers for lineage assignment, these often fail to capture the dynamic biological behavior of the malignant clone. This review synthesizes studies on the integration of functional biomarkers, specifically the nuclear proliferation marker Ki-67 and the anti-apoptotic protein Bcl-2, into the diagnostic and prognostic workflow. By utilizing high-dimensional multiparameter flow cytometry (MFC) and software-based maturation continuum analysis, the survival and growth kinetics of the myeloid, erythroid, and monocytic lineages can be quantified. These findings redefine myelodysplastic syndromes (MDS) as characterized by a significant decrease in cell-cycle progression and an increase in anti-apoptotic activity during early stages of maturation. Recent studies demonstrate that integrating the erythroid Ki-67 proliferation index as a fifth parameter into the conventional Ogata score dramatically improves diagnostic sensitivity for detecting MDS from 66% to 90% while maintaining 100% specificity. In particular, the sensitivity for detecting low-grade MDS improved from 56% to 91%. Additionally, a reduced erythroid Ki-67 index (≤28%) is a powerful independent predictor of transfusion dependence within 1 year. Beyond diagnostics, the introduction of the Bcl-2:Ki-67 ratio provides a superior metric for biological aggressiveness and a potential predictive tool for precision medicine. A high ratio identifies a quiescent, apoptosis-resistant cell population that is likely refractory to standard chemotherapy but is an ideal candidate for targeted Bcl-2 inhibition with Venetoclax. The integration of functional biomarkers bridges the gap between complex mutational landscapes and clinical manifestations. While digital imaging and artificial intelligence (AI) are beginning to automate blast enumeration and maturation analysis, functional kinetics may provide a necessary biological readout for personalized therapy.

Indexed as

apoptosisBcl-2Ki-67multiparameter flow cytometrymyelodysplastic syndromeprecision medicineproliferationVenetoclax

Identifiers

PMID42649960
PMCPMC13510372

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.