Topical Collection "Innovations in Cancer Diagnostic Evaluation and Biomarker Detection"

A topical collection in Cancers (ISSN 2072-6694). This collection belongs to the section "Cancer Biomarkers".

Editor

Prof. Dr. Joseph D. Khoury
E-Mail Website
Guest Editor
Division of Pathology/Lab Medicine, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: leukemia; lymphoma; cancer biomarkers

Topical Collection Information

Dear colleagues,

The pace of innovations in laboratory techniques for cancer diagnosis, biomarker detection, and disease monitoring has expanded significantly over the past decade. Such innovations currently permit an unprecedented level of nuance and depth in terms of disease classification and detection of therapy targets across the continuum of cancer care. Since laboratory innovations currently form the basis of risk stratification and therapy selection in a broad array of cancers, understanding their strengths and limitations has become critical for informed treatment decisions.

This Special Issue will be focused on novel technologies and laboratory approaches employed in the diagnosis and classification of cancer, as well as the detection of tissue- and blood-based biomarkers that inform treatment decisions. We welcome research papers as well as expert reviews that shed light on the state-of-the-art of this critical area underpinning cancer care today.

Prof. Dr. Joseph D. Khoury
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the collection website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer
  • biomarker
  • laboratory techniques
  • pathology
  • tissue

Published Papers (14 papers)

2021

Jump to: 2020

Review
Potential Biomarkers for Treatment Response to the BCL-2 Inhibitor Venetoclax: State of the Art and Future Directions
Cancers 2021, 13(12), 2974; https://doi.org/10.3390/cancers13122974 - 14 Jun 2021
Viewed by 619
Abstract
Intrinsic apoptotic pathway dysregulation plays an essential role in all cancers, particularly hematologic malignancies. This role has led to the development of multiple therapeutic agents targeting this pathway. Venetoclax is a selective BCL-2 inhibitor that has been approved for the treatment of chronic [...] Read more.
Intrinsic apoptotic pathway dysregulation plays an essential role in all cancers, particularly hematologic malignancies. This role has led to the development of multiple therapeutic agents targeting this pathway. Venetoclax is a selective BCL-2 inhibitor that has been approved for the treatment of chronic lymphoid leukemia and acute myeloid leukemia. Given the reported resistance to venetoclax, understanding the mechanisms of resistance and the potential biomarkers of response is crucial to ensure optimal drug usage and improved patient outcomes. Mechanisms of resistance to venetoclax include alterations involving the BH3-binding groove, BCL2 gene mutations affecting venetoclax binding, and activation of alternative anti-apoptotic pathways. Moreover, various potential genetic biomarkers of venetoclax resistance have been proposed, including chromosome 17p deletion, trisomy 12, and TP53 loss or mutation. This manuscript provides an overview of biomarkers that could predict treatment response to venetoclax. Full article
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Article
T-Cell Lymphoma Clonality by Copy Number Variation Analysis of T-Cell Receptor Genes
Cancers 2021, 13(2), 340; https://doi.org/10.3390/cancers13020340 - 19 Jan 2021
Viewed by 1185
Abstract
T-cell lymphomas arise from a single neoplastic clone and exhibit identical patterns of deletions in T-cell receptor (TCR) genes. Whole genome sequencing (WGS) data represent a treasure trove of information for the development of novel clinical applications. However, the use of WGS to [...] Read more.
T-cell lymphomas arise from a single neoplastic clone and exhibit identical patterns of deletions in T-cell receptor (TCR) genes. Whole genome sequencing (WGS) data represent a treasure trove of information for the development of novel clinical applications. However, the use of WGS to identify clonal T-cell proliferations has not been systematically studied. In this study, based on WGS data, we identified monoclonal rearrangements (MRs) of T-cell receptors (TCR) genes using a novel segmentation algorithm and copy number computation. We evaluated the feasibility of this technique as a marker of T-cell clonality using T-cell lymphomas (TCL, n = 44) and extranodal NK/T-cell lymphomas (ENKTLs, n = 20), and identified 98% of TCLs with one or more TCR gene MRs, against 91% detected using PCR. TCR MRs were absent in all ENKTLs and NK cell lines. Sensitivity-wise, this platform is sufficiently competent, with MRs detected in the majority of samples with tumor content under 25% and it can also distinguish monoallelic from biallelic MRs. Understanding the copy number landscape of TCR using WGS data may engender new diagnostic applications in hematolymphoid pathology, which can be readily adapted to the analysis of B-cell receptor loci for B-cell clonality determination. Full article
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2020

Jump to: 2021

Article
Sequential Colocalization of ERa, PR, and AR Hormone Receptors Using Confocal Microscopy Enables New Insights into Normal Breast and Prostate Tissue and Cancers
Cancers 2020, 12(12), 3591; https://doi.org/10.3390/cancers12123591 - 30 Nov 2020
Cited by 1 | Viewed by 658
Abstract
Multiplex immunohistochemistry (mIHC) use markers staining different cell populations applying widefield optical microscopy. Resolution is low not resolving subcellular co-localization. We sought to colocalize markers at subcellular level with antibodies validated for clinical diagnosis, including the single secondary antibody (combination of anti-rabbit/mouse-antibodies) used [...] Read more.
Multiplex immunohistochemistry (mIHC) use markers staining different cell populations applying widefield optical microscopy. Resolution is low not resolving subcellular co-localization. We sought to colocalize markers at subcellular level with antibodies validated for clinical diagnosis, including the single secondary antibody (combination of anti-rabbit/mouse-antibodies) used for diagnostic IHC with any primary antibody, and confocal microscopy. We explore colocalization in the nucleus (ColNu) of nuclear hormone receptors (ERa, PR, and AR) along with the baseline marker p63 in paired samples of breast and prostate tissues. We established ColNu mIHCF as a reliable technique easily implemented in a hospital setting. In ERa+ breast cancer, we identified different colocalization patterns (nuclear or cytoplasmatic) with PR and AR on the luminal epithelium. A triple-negative breast-cancer case expressed membrane-only ERa. A PR-only case was double positive PR/p63. In normal prostate, we identified an ERa+/p63+/AR-negative distinct population. All prostate cancer cases characteristically expressed ERa on the apical membrane of the AR+ epithelium. We confirmed this using ERa IHC and needle-core biopsies. ColNu mIHCF is feasible and already revealed a new marker for prostate cancer and identified sub-patterns in breast cancer. It could be useful for pathology as well as for functional studies in normal prostate and breast tissues. Full article
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Article
Contrast-Enhanced Mammography for Screening Women after Breast Conserving Surgery
Cancers 2020, 12(12), 3495; https://doi.org/10.3390/cancers12123495 - 24 Nov 2020
Cited by 1 | Viewed by 499
Abstract
To investigate the value of contrast-enhanced mammography (CEM) compared to full-field digital mammography (FFDM) in screening breast cancer patients after breast-conserving surgery (BCS), this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved retrospective, single-institution study included 971 CEM exams in 541 asymptomatic [...] Read more.
To investigate the value of contrast-enhanced mammography (CEM) compared to full-field digital mammography (FFDM) in screening breast cancer patients after breast-conserving surgery (BCS), this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved retrospective, single-institution study included 971 CEM exams in 541 asymptomatic patients treated with BCS who underwent screening CEM between January 2013 and November 2018. Histopathology, or at least a one-year follow-up, was used as the standard of reference. Twenty-one of 541 patients (3.9%) were diagnosed with ipsi- or contralateral breast cancer: six (28.6%) cancers were seen with low-energy images (equivalent to FFDM), an additional nine (42.9%) cancers were detected only on iodine (contrast-enhanced) images, and six interval cancers were identified within 365 days of a negative screening CEM. Of the 10 ipsilateral cancers detected on CEM, four were detected on low-energy images (40%). Of the five contralateral cancers detected on CEM, two were detected on low-energy images (40%). Overall, the cancer detection rate (CDR) for CEM was 15.4/1000 (15/971), and the positive predictive value (PPV3) of the biopsies performed was 42.9% (15/35). For findings seen on low-energy images, with or without contrast, the CDR was 6.2/1000 (6/971), and the PPV3 of the biopsies performed was 37.5% (6/16). In the post-BCS screening setting, CEM has a higher CDR than FFDM. Full article
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Review
CD123 as a Biomarker in Hematolymphoid Malignancies: Principles of Detection and Targeted Therapies
Cancers 2020, 12(11), 3087; https://doi.org/10.3390/cancers12113087 - 23 Oct 2020
Cited by 2 | Viewed by 900
Abstract
CD123, the α chain of the interleukin 3 receptor, is a cytokine receptor that is overexpressed in multiple hematolymphoid neoplasms, including acute myeloid leukemia, blastic plasmacytoid dendritic cell neoplasm, acute lymphoblastic leukemia, hairy cell leukemia, and systemic mastocytosis. Importantly, CD123 expression is upregulated [...] Read more.
CD123, the α chain of the interleukin 3 receptor, is a cytokine receptor that is overexpressed in multiple hematolymphoid neoplasms, including acute myeloid leukemia, blastic plasmacytoid dendritic cell neoplasm, acute lymphoblastic leukemia, hairy cell leukemia, and systemic mastocytosis. Importantly, CD123 expression is upregulated in leukemic stem cells relative to non-neoplastic hematopoietic stem cells, which makes it a useful diagnostic and therapeutic biomarker in hematologic malignancies. Varying levels of evidence have shown that CD123-targeted therapy represents a promising therapeutic approach in several cancers. Tagraxofusp, an anti-CD123 antibody conjugated to a diphtheria toxin, has been approved for use in patients with blastic plasmacytoid dendritic cell neoplasm. Multiple clinical trials are investigating the use of various CD123-targeting agents, including chimeric antigen receptor-modified T cells (expressing CD123, monoclonal antibodies, combined CD3-CD123 dual-affinity retargeting antibody therapy, recombinant fusion proteins, and CD123-engager T cells. In this review, we provide an overview of laboratory techniques used to evaluate and monitor CD123 expression, describe the strengths and limitations of detecting this biomarker in guiding therapy decisions, and provide an overview of the pharmacologic principles and strategies used in CD123-targeted therapies. Full article
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Review
Aggressive NK Cell Leukemia: Current State of the Art
Cancers 2020, 12(10), 2900; https://doi.org/10.3390/cancers12102900 - 09 Oct 2020
Cited by 3 | Viewed by 932
Abstract
Aggressive natural killer (NK) cell leukemia (ANKL) is a rare disease with a grave prognosis. Patients commonly present acutely with fever, constitutional symptoms, hepatosplenomegaly, and often disseminated intravascular coagulation or hemophagocytic syndrome. This acute clinical presentation and the variable pathologic and immunophenotypic features [...] Read more.
Aggressive natural killer (NK) cell leukemia (ANKL) is a rare disease with a grave prognosis. Patients commonly present acutely with fever, constitutional symptoms, hepatosplenomegaly, and often disseminated intravascular coagulation or hemophagocytic syndrome. This acute clinical presentation and the variable pathologic and immunophenotypic features of ANKL overlap with other diagnostic entities, making it challenging to establish a timely and accurate diagnosis of ANKL. Since its original recognition in 1986, substantial progress in understanding this disease using traditional pathologic approaches has improved diagnostic accuracy. This progress, in turn, has facilitated the performance of recent high-throughput studies that have yielded insights into pathogenesis. Molecular abnormalities that occur in ANKL can be divided into three major groups: JAK/STAT pathway activation, epigenetic dysregulation, and impairment of TP53 and DNA repair. These high-throughput data also have provided potential therapeutic targets that promise to improve therapy and outcomes for patients with ANKL. In this review, we provide a historical context of the conception and evolution of ANKL as a disease entity, we highlight advances in diagnostic criteria to recognize this disease, and we review recent understanding of pathogenesis as well as biomarker discoveries that are providing groundwork for innovative therapies. Full article
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Comment
Comment on Aasebø, E., et al. “The Progression of Acute Myeloid Leukemia from First Diagnosis to Chemoresistant Relapse: A Comparison of Proteomic and Phosphoproteomic Profiles”. Cancers 2020, 12, 1466
Cancers 2020, 12(9), 2461; https://doi.org/10.3390/cancers12092461 - 31 Aug 2020
Cited by 2 | Viewed by 419
Abstract
In a recent article published in this journal, Aasebø and colleagues reported [...] Full article
Article
Feasibility, Image Quality and Clinical Evaluation of Contrast-Enhanced Breast MRI Performed in a Supine Position Compared to the Standard Prone Position
Cancers 2020, 12(9), 2364; https://doi.org/10.3390/cancers12092364 - 21 Aug 2020
Cited by 1 | Viewed by 577
Abstract
Background: To assess the feasibility, image quality and diagnostic value of contrast-enhanced breast magnetic resonance imaging (MRI) performed in a supine compared to a prone position. Methods: One hundred and fifty-one patients who had undergone a breast MRI in both the standard prone [...] Read more.
Background: To assess the feasibility, image quality and diagnostic value of contrast-enhanced breast magnetic resonance imaging (MRI) performed in a supine compared to a prone position. Methods: One hundred and fifty-one patients who had undergone a breast MRI in both the standard prone and supine position were evaluated retrospectively. Two 1.5 T MR scanners were used with the same image resolution, sequences and contrast medium in all examinations. The image quality and the number and dimensions of lesions were assessed by two expert radiologists in an independent and randomized fashion. Two different classification systems were used. Histopathology was the standard of reference. Results: Two hundred and forty MRIs from 120 patients were compared. The analysis revealed 134 MRIs with monofocal (U), 68 with multifocal (M) and 38 with multicentric (C) lesions. There was no difference between the image quality and number of lesions in the prone and supine examinations. A significant difference in the lesion extension was observed between the prone and supine position. No significant differences emerged in the classification of the lesions detected in the prone compared to the supine position. Conclusions: It is possible to perform breast MRI in a supine position with the same image quality, resolution and diagnostic value as in a prone position. In the prone position, the lesion dimensions are overestimated with a higher wash-in peak than in the supine position. Full article
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Article
Discovery of Prognostic Markers for Early-Stage High-Grade Serous Ovarian Cancer by Maldi-Imaging
Cancers 2020, 12(8), 2000; https://doi.org/10.3390/cancers12082000 - 22 Jul 2020
Cited by 2 | Viewed by 878
Abstract
With regard to relapse and survival, early-stage high-grade serous ovarian (HGSOC) patients comprise a heterogeneous group and there is no clear consensus on first-line treatment. Currently, no prognostic markers are available for risk assessment by standard targeted immunohistochemistry and novel approaches are urgently [...] Read more.
With regard to relapse and survival, early-stage high-grade serous ovarian (HGSOC) patients comprise a heterogeneous group and there is no clear consensus on first-line treatment. Currently, no prognostic markers are available for risk assessment by standard targeted immunohistochemistry and novel approaches are urgently required. Here, we applied MALDI-imaging mass spectrometry (MALDI-IMS), a new method to identify distinct mass profiles including protein signatures on paraffin-embedded tissue sections. In search of prognostic biomarker candidates, we compared proteomic profiles of primary tumor sections from early-stage HGSOC patients with either recurrent (RD) or non-recurrent disease (N = 4; each group) as a proof of concept study. In total, MALDI-IMS analysis resulted in 7537 spectra from the malignant tumor areas. Using receiver operating characteristic (ROC) analysis, 151 peptides were able to discriminate between patients with RD and non-RD (AUC > 0.6 or < 0.4; p < 0.01), and 13 of them could be annotated to proteins. Strongest expression levels of specific peptides linked to Keratin type1 and Collagen alpha-2(I) were observed and associated with poor prognosis (AUC > 0.7). These results confirm that in using IMS, we could identify new candidates to predict clinical outcome and treatment extent for patients with early-stage HGSOC. Full article
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Communication
Gene Pair Correlation Coefficients in Sphingolipid Metabolic Pathway as a Potential Prognostic Biomarker for Breast Cancer
Cancers 2020, 12(7), 1747; https://doi.org/10.3390/cancers12071747 - 01 Jul 2020
Cited by 3 | Viewed by 1248
Abstract
Complex diseases such as cancer are usually governed by dynamic and simultaneous modifications of multiple genes. Since sphingolipids are potent bioactive molecules and regulate many important pathophysiological processes such as carcinogenesis, we studied the gene pair correlations of 36 genes (31 genes in [...] Read more.
Complex diseases such as cancer are usually governed by dynamic and simultaneous modifications of multiple genes. Since sphingolipids are potent bioactive molecules and regulate many important pathophysiological processes such as carcinogenesis, we studied the gene pair correlations of 36 genes (31 genes in the sphingolipid metabolic pathway and 5 genes encoding the sphingosine-1-phosphate receptors) between breast cancer patients and healthy controls. It is remarkable to observe that the gene expressions were widely and strongly correlated in healthy controls but in general lost in breast cancer patients. This study suggests that gene pair correlation coefficients could be applied as a systematic and novel method for the diagnosis and prognosis of breast cancer. Full article
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Communication
The Progression of Acute Myeloid Leukemia from First Diagnosis to Chemoresistant Relapse: A Comparison of Proteomic and Phosphoproteomic Profiles
Cancers 2020, 12(6), 1466; https://doi.org/10.3390/cancers12061466 - 04 Jun 2020
Cited by 9 | Viewed by 1224
Abstract
Acute myeloid leukemia (AML) is an aggressive hematological malignancy. Nearly 50% of the patients who receive the most intensive treatment develop chemoresistant leukemia relapse. Although the leukemogenic events leading to relapse seem to differ between patients (i.e., regrowth from a clone detected at [...] Read more.
Acute myeloid leukemia (AML) is an aggressive hematological malignancy. Nearly 50% of the patients who receive the most intensive treatment develop chemoresistant leukemia relapse. Although the leukemogenic events leading to relapse seem to differ between patients (i.e., regrowth from a clone detected at first diagnosis, progression from the original leukemic or preleukemic stem cells), a common characteristic of relapsed AML is increased chemoresistance. The aim of the present study was to investigate at the proteomic level whether leukemic cells from relapsed patients present overlapping molecular mechanisms that contribute to this chemoresistance. We used liquid chromatography–tandem mass spectrometry (LC–MS/MS) to compare the proteomic and phosphoproteomic profiles of AML cells derived from seven patients at the time of first diagnosis and at first relapse. At the time of first relapse, AML cells were characterized by increased levels of proteins important for various mitochondrial functions, such as mitochondrial ribosomal subunit proteins (MRPL21, MRPS37) and proteins for RNA processing (DHX37, RNA helicase; RPP40, ribonuclease P component), DNA repair (ERCC3, DNA repair factor IIH helicase; GTF2F1, general transcription factor), and cyclin-dependent kinase (CDK) activity. The levels of several cytoskeletal proteins (MYH14/MYL6/MYL12A, myosin chains; VCL, vinculin) as well as of proteins involved in vesicular trafficking/secretion and cell adhesion (ITGAX, integrin alpha-X; CD36, platelet glycoprotein 4; SLC2A3, solute carrier family 2) were decreased in relapsed cells. Our study introduces new targetable proteins that might direct therapeutic strategies to decrease chemoresistance in relapsed AML. Full article
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Article
Classification of Breast Cancer Cells Using the Integration of High-Frequency Single-Beam Acoustic Tweezers and Convolutional Neural Networks
Cancers 2020, 12(5), 1212; https://doi.org/10.3390/cancers12051212 - 12 May 2020
Cited by 2 | Viewed by 944
Abstract
Single-beam acoustic tweezers (SBAT) is a widely used trapping technique to manipulate microscopic particles or cells. Recently, the characterization of a single cancer cell using high-frequency (>30 MHz) SBAT has been reported to determine its invasiveness and metastatic potential. Investigation of cell elasticity [...] Read more.
Single-beam acoustic tweezers (SBAT) is a widely used trapping technique to manipulate microscopic particles or cells. Recently, the characterization of a single cancer cell using high-frequency (>30 MHz) SBAT has been reported to determine its invasiveness and metastatic potential. Investigation of cell elasticity and invasiveness is based on the deformability of cells under SBAT’s radiation forces, and in general, more physically deformed cells exhibit higher levels of invasiveness and therefore higher metastatic potential. However, previous imaging analysis to determine substantial differences in cell deformation, where the SBAT is turned ON or OFF, relies on the subjective observation that may vary and requires follow-up evaluations from experts. In this study, we propose an automatic and reliable cancer cell classification method based on SBAT and a convolutional neural network (CNN), which provides objective and accurate quantitative measurement results. We used a custom-designed 50 MHz SBAT transducer to obtain a series of images of deformed human breast cancer cells. CNN-based classification methods with data augmentation applied to collected images determined and validated the metastatic potential of cancer cells. As a result, with the selected optimizers, precision, and recall of the model were found to be greater than 0.95, which highly validates the classification performance of our integrated method. CNN-guided cancer cell deformation analysis using SBAT may be a promising alternative to current histological image analysis, and this pretrained model will significantly reduce the evaluation time for a larger population of cells. Full article
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Review
The Role of Deubiquitinating Enzymes in Hematopoiesis and Hematological Malignancies
Cancers 2020, 12(5), 1103; https://doi.org/10.3390/cancers12051103 - 28 Apr 2020
Cited by 2 | Viewed by 1217
Abstract
Hematopoietic stem cells (HSCs) are responsible for the production of blood cells throughout the human lifespan. Single HSCs can give rise to at least eight distinct blood-cell lineages. Together, hematopoiesis, erythropoiesis, and angiogenesis coordinate several biological processes, i.e., cellular interactions during development and [...] Read more.
Hematopoietic stem cells (HSCs) are responsible for the production of blood cells throughout the human lifespan. Single HSCs can give rise to at least eight distinct blood-cell lineages. Together, hematopoiesis, erythropoiesis, and angiogenesis coordinate several biological processes, i.e., cellular interactions during development and proliferation, guided migration, lineage programming, and reprogramming by transcription factors. Any dysregulation of these processes can result in hematological disorders and/or malignancies. Several studies of the molecular mechanisms governing HSC maintenance have demonstrated that protein regulation by the ubiquitin proteasomal pathway is crucial for normal HSC function. Recent studies have shown that reversal of ubiquitination by deubiquitinating enzymes (DUBs) plays an equally important role in hematopoiesis; however, information regarding the biological function of DUBs is limited. In this review, we focus on recent discoveries about the physiological roles of DUBs in hematopoiesis, erythropoiesis, and angiogenesis and discuss the DUBs associated with common hematological disorders and malignancies, which are potential therapeutic drug targets. Full article
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Article
Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia
Cancers 2020, 12(3), 709; https://doi.org/10.3390/cancers12030709 - 17 Mar 2020
Cited by 10 | Viewed by 1609
Abstract
Acute myeloid leukemia (AML) is a hematological cancer that mainly affects the elderly. Although complete remission (CR) is achieved for the majority of the patients after induction and consolidation therapies, nearly two-thirds relapse within a short interval. Understanding biological factors that determine relapse [...] Read more.
Acute myeloid leukemia (AML) is a hematological cancer that mainly affects the elderly. Although complete remission (CR) is achieved for the majority of the patients after induction and consolidation therapies, nearly two-thirds relapse within a short interval. Understanding biological factors that determine relapse has become of major clinical interest in AML. We utilized liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify the protein changes and protein phosphorylation events associated with AML relapse in primary cells from 41 AML patients at time of diagnosis. Patients were defined as relapse-free if they had not relapsed within a five-year clinical follow-up after AML diagnosis. Relapse was associated with increased expression of RNA processing proteins and decreased expression of V-ATPase proteins. We also observed an increase in phosphorylation events catalyzed by cyclin-dependent kinases (CDKs) and casein kinase 2 (CSK2). The biological relevance of the proteome findings was supported by cell proliferation assays using inhibitors of V-ATPase (bafilomycin), CSK2 (CX-4945), CDK4/6 (abemaciclib) and CDK2/7/9 (SNS-032). While bafilomycin preferentially inhibited the cells from relapse patients, the kinase inhibitors were less efficient in these cells. This suggests that therapy against the upregulated kinases could also target the factors inducing their upregulation rather than their activity. This study, therefore, presents markers that could help predict AML relapse and direct therapeutic strategies. Full article
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