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Biomedicines
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Pathogenesis, Diagnosis and Treatment of Hematologic Malignancies
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Pathogenesis, Diagnosis and Treatment of Hematologic Malignancies

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 30 September 2025 | Viewed by 4555

Special Issue Editor

Dr. Michele Gottardi

E-Mail Website
Guest Editor
Onco Hematology, Department of Oncology, Veneto Institute of Oncology IOV, IRCCS, 31033 Padua, Italy
Interests: AML; core binding factor AML; novel agents; bone marrow microenviroment; HSCT
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hematologic malignancies represent a heterogeneous group of diseases that can have overlapping clinical manifestations, and their successful and optimal management relies on early and accurate diagnosis. Historically, hematologic malignancies played a role in the pioneering use of genetic analyses for diagnoses, prognoses, and therapeutic decision-making. Furthermore, the precise definition of the pathogenesis (thanks to advanced molecular techniques) has allowed us to understand the biologic basis of these diseases, ultimately leading to the development of several targeted therapies. Future research should focus on increasingly defining the genetic pathways with the aim of identifying and validating new therapeutic targets and rapidly translating them into clinical trials. In the present Special Issue, we invite authors to submit original research papers and reviews on how increasingly in-depth knowledge of the pathogenesis, diagnosis, and ultimately treatment of hematologic malignancies may improve patient outcomes.

Dr. Michele Gottardi
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 submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue 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.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 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

  • hematologic malignancies
  • pathogenesis
  • diagnosis
  • treatment
  • targeted therapy
  • molecular research

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Published Papers (5 papers)

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Research

14 pages, 1789 KiB  
Article
Development and Validation of a Predictive Nomogram for Venous Thromboembolism Risk in Multiple Myeloma Patients: A Single-Center Cohort Study in China
by Haolin Zhang, Xi Zhang, Xiaosheng Li, Qianjie Xu, Yuliang Yuan, Zuhai Hu, Yulan Zhao, Yao Liu, Yunyun Zhang and Haike Lei
Biomedicines 2025, 13(4), 770; https://doi.org/10.3390/biomedicines13040770 - 21 Mar 2025
Viewed by 313
Abstract
Objectives: Venous thromboembolism (VTE) is a significant complication in patients with multiple myeloma (MM) that adversely affects morbidity, mortality, and treatment outcomes. This study aimed to develop and validate a predictive nomogram for assessing VTE risk in MM patients using clinicopathological factors. Methods: [...] Read more.
Objectives: Venous thromboembolism (VTE) is a significant complication in patients with multiple myeloma (MM) that adversely affects morbidity, mortality, and treatment outcomes. This study aimed to develop and validate a predictive nomogram for assessing VTE risk in MM patients using clinicopathological factors. Methods: Clinical data, including 25 candidate risk factors, were collected. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for VTE. The nomogram was constructed using these variables, and its performance was evaluated by plotting receiver operating characteristic (ROC) curves, calculating the area under the curve (AUC), and conducting calibration and decision curve analysis (DCA). Additionally, an online calculator was developed for clinical use. Results: In total, 148 patients (17.5%) developed VTE in this study. The independent risk factors included age, Karnofsky performance status (KPS), anticoagulation therapy, erythropoietin use, and hemoglobin (Hb), platelet (PLT), calcium (Ca), activated partial thromboplastin time (APTT), and D-dimer levels. The nomogram demonstrated robust discriminative ability, with a C-index of 0.811 in the training cohort and 0.714 in the validation cohort. The calibration curves exhibited a high level of agreement between the predicted and observed probabilities. DCA confirmed the nomogram’s clinical utility across various threshold ranges, outperforming the “treat all” and “treat none” strategies. Conclusions: This study successfully developed and validated a nomogram for predicting VTE risk in MM patients, demonstrating substantial predictive accuracy and clinical applicability. The nomogram and accompanying online calculator provide valuable tools for individualized VTE risk assessment and informed clinical decision-making. Full article
(This article belongs to the Special Issue Pathogenesis, Diagnosis and Treatment of Hematologic Malignancies)
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17 pages, 3084 KiB  
Article
COMMD3 Regulates Copper Metabolism via the ATOX1-ATP7A-LOX Axis to Promote Multiple Myeloma Progression
by Yajun Wang, Bo Zhang, Fengjuan Fan, Fei Zhao, Jian Xu, Yuhuan Zheng, Chunyan Sun and Yu Hu
Biomedicines 2025, 13(2), 351; https://doi.org/10.3390/biomedicines13020351 - 4 Feb 2025
Viewed by 989
Abstract
Background: Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells, with extramedullary myeloma (EMM) being an aggressive form involving malignant infiltration beyond the bone marrow. Copper metabolism is essential for tumor proliferation and metastasis, with copper metabolism [...] Read more.
Background: Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells, with extramedullary myeloma (EMM) being an aggressive form involving malignant infiltration beyond the bone marrow. Copper metabolism is essential for tumor proliferation and metastasis, with copper metabolism MURR1 domain (COMMD) proteins regulating these processes and maintaining copper homeostasis. Dysregulated copper homeostasis contributes to cancer progression, including MM, with elevated copper levels linked to disease aggressiveness and poor prognosis. This study investigates the role of the COMMD3 in mediating MM cell progression, particularly its influence on copper metabolism. Methods: Comprehensive bioinformatics analyses were conducted on bone marrow and extramedullary samples to determine the expression of COMMD3, which was validated through in vitro and in vivo functional assays. The MM cell lines RPMI8226 and MM1S underwent lentiviral transfection for COMMD3 overexpression and knockdown. RNA sequencing was conducted on COMMD3 knockdown cells to identify differentially expressed genes. Functional assays measured cell proliferation, migration, apoptosis, and copper metabolism, with a non-obese diabetic severe combined immune-deficiency gamma (NSG) mouse xenograft model providing in vivo validation. Results: Elevated COMMD3 expression was correlated with extramedullary myeloma and poor prognosis in MM patients. COMMD3 promoted MM cell proliferation and migration, modulating intracellular copper levels, likely through the ATOX1-ATP7A-LOX copper-metabolism-related pathway. High ATOX1 expression was correlated with worse outcomes, and ATOX1 inhibition abolished COMMD3’s effects. Conclusions: This study highlights the pivotal role of COMMD3 in MM progression, particularly via the ATOX1-ATP7A-LOX axis. These findings provide insights into EMM mechanisms and position COMMD3 as a potential therapeutic target. Future research is needed to validate these findings in larger clinical cohorts and to unravel the precise molecular interactions between COMMD3 and copper metabolism proteins. Full article
(This article belongs to the Special Issue Pathogenesis, Diagnosis and Treatment of Hematologic Malignancies)
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10 pages, 2138 KiB  
Article
A Nomogram Built on Clinical Factors and CT Attenuation Scores for Predicting Treatment Response of Acute Myeloid Leukemia Patients
by Linna Liu, Wenzheng Lu, Li Xiong, Han Qi, Robert Peter Gale and Bin Yin
Biomedicines 2025, 13(1), 198; https://doi.org/10.3390/biomedicines13010198 - 15 Jan 2025
Viewed by 827
Abstract
Background: Acute myeloid leukemia (AML) is an aggressive cancer with variable treatment responses. While clinical factors such as age and genetic mutations contribute to prognosis, recent studies suggest that CT attenuation scores may also predict treatment outcomes. This study aims to develop a [...] Read more.
Background: Acute myeloid leukemia (AML) is an aggressive cancer with variable treatment responses. While clinical factors such as age and genetic mutations contribute to prognosis, recent studies suggest that CT attenuation scores may also predict treatment outcomes. This study aims to develop a nomogram combining clinical and CT-based factors to predict treatment response and guide personalized therapy for AML patients. Methods: This retrospective study included 74 newly diagnosed AML patients who underwent unenhanced abdominal CT scans within one week before receiving their first induction chemotherapy. Clinical biomarkers of tumor burden were also collected. Patients were classified into two groups based on treatment response: complete remission (CR; n = 24) and non-complete remission (NCR; n = 50). Multivariable logistic regression was used to identify independent predictors of treatment response. Predictive performance was evaluated using receiver operating characteristic (ROC) curves, and model consistency was assessed through calibration and decision curve analysis (DCA). Results: Significant differences in hemoglobin (Hb), platelets (Plt), and CT attenuation scores were observed between the CR and NCR groups (all p < 0.05). Multivariable logistic regression identified Hb, Plt, and CT attenuation scores as independent predictors of treatment response. A nomogram incorporating these factors demonstrated excellent predictive performance, with an area under the curve (AUC) of 0.912 (95% CI: 0.842–0.983), accuracy of 0.865 (95% CI: 0.765–0.933), sensitivity of 0.880 (95% CI: 0.790–0.970), and specificity of 0.833 (95% CI: 0.684–0.982). The CR nomogram displayed significant clinical value and excellent goodness of fit. Conclusions: The nomogram, which incorporates Hb, Plt, and CT attenuation scores, provides valuable insights into predicting treatment response in AML patients. This model offers strong discriminatory ability and could enhance personalized treatment planning and prognosis prediction for AML. Full article
(This article belongs to the Special Issue Pathogenesis, Diagnosis and Treatment of Hematologic Malignancies)
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14 pages, 1640 KiB  
Article
Impact of First- and Second-Generation Tyrosine Kinase Inhibitors on the Development of Graft-Versus-Host Disease in Individuals with Chronic Myeloid Leukemia: A Retrospective Analysis on Behalf of the Polish Adult Leukemia Group
by Ugo Giordano, Agnieszka Piekarska, Witold Prejzner, Lidia Gil, Jan Maciej Zaucha, Joanna Kujawska, Zuzanna Dybko, Krzysztof Dudek, Sebastian Giebel and Jarosław Dybko
Biomedicines 2025, 13(1), 163; https://doi.org/10.3390/biomedicines13010163 - 11 Jan 2025
Viewed by 1137
Abstract
Background: The implementation of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) has brought a significant improvement in the prognosis for CML patients and a decrease in the number of patients requiring allogeneic hematopoietic stem cell transplantation (allo-HCT). [...] Read more.
Background: The implementation of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) has brought a significant improvement in the prognosis for CML patients and a decrease in the number of patients requiring allogeneic hematopoietic stem cell transplantation (allo-HCT). Nevertheless, the impact of TKIs on allo-HCT outcomes has not been thoroughly explored. Objectives: The main endpoint of our research was to assess the impact of prior TKI treatment on acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD). Methods: In our retrospective analysis, we included 240 patients treated between 1993 and 2013 and divided them into three groups according to the therapy administered prior to haploidentical, matched-related, or matched-unrelated donor allo-HCT (imatinib group n = 41, dasatinib/nilotinib group n = 28, TKI-naïve group n = 171). Results: Both the cumulative incidence of aGvHD (p = 0.044) and cGvHD (p < 0.001) in individuals receiving second-generation TKIs (2G-TKIs) prior to allo-HCT were decreased compared to patients receiving no TKIs or imatinib (IMA) (40.7% vs. 61.4% vs. 70.7%, p = 0.044; 25.0% vs. 76.4% vs. 51.2%, p < 0.001, respectively). In the case of the 2G-TKI cohort, the number of low-grade aGvHD and cGvHD was significantly lower compared to the IMA and TKI-naïve groups (p = 0.018, p = 0.004; p < 0.001 versus TKI-naïve, respectively). In terms of 3-year overall survival (OS), there were no important variations between TKI-naïve, IMA, and 2G-TKI (55% vs. 49.9% vs. 69.6%, p = 0.740). Conclusions: The results of our study suggest that TKI treatment prior to allo-HCT may have a protective impact on immune-mediated outcomes. Full article
(This article belongs to the Special Issue Pathogenesis, Diagnosis and Treatment of Hematologic Malignancies)
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13 pages, 2303 KiB  
Article
Early Identification of the Non-Transplanted Functional High-Risk Multiple Myeloma: Insights from a Predictive Nomogram
by Yanjuan Li, Lifen Kuang, Beihui Huang, Junru Liu, Meilan Chen, Xiaozhe Li, Jingli Gu, Tongyong Yu and Juan Li
Biomedicines 2025, 13(1), 145; https://doi.org/10.3390/biomedicines13010145 - 9 Jan 2025
Viewed by 629
Abstract
Background: Patients with multiple myeloma (MM) who have a suboptimal response to induction therapy or early relapse are classified as functional high-risk (FHR) patients and have been shown to have a dismal prognosis. The aim of this study was to establish a [...] Read more.
Background: Patients with multiple myeloma (MM) who have a suboptimal response to induction therapy or early relapse are classified as functional high-risk (FHR) patients and have been shown to have a dismal prognosis. The aim of this study was to establish a predictive nomogram for patients with non-transplanted FHR MM. Materials and Methods: The group comprised 215 patients in our center between 1 January 2006 and 1 March 2024. To identify independent risk factors, univariate and multivariate logistic regression analyses were performed, and a nomogram was constructed to predict non-transplant FHR MM. To evaluate the nomogram’s predictive accuracy, we utilized bias-corrected AUC, calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC). Results: Multivariate logistic regression demonstrated that younger age at onset, a higher proportion of LDH (more than 220 U/L), pattern A + C of M protein decline patterns, a lower proportion of patients with induction treatment efficacy than VGPR, and those undergoing maintenance therapies were independent risk factors for patients with non-transplanted FHR MM. The AUC scores for the training and internal validation groups were 0.940 (95% CI 0.893–0.986) and 0.978 (95% CI 0.930–1.000). DCA and CIC curves were utilized to further verify the clinical efficacy of the nomogram. Conclusions: We developed a nomogram that enables early prediction of non-transplant FHR MM patients. Younger age at onset, LDH ≥ 220 U/L, an A + C pattern of M-protein decline, and induction therapy efficacy not reaching VGPR are more likely to be FHR MM patients. Patients who do not undergo maintenance therapy are prone to early progression or relapse. Full article
(This article belongs to the Special Issue Pathogenesis, Diagnosis and Treatment of Hematologic Malignancies)
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