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Hematologic Malignancies: From Molecular Pathology to Novel Therapeutics
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Hematologic Malignancies: From Molecular Pathology to Novel Therapeutics

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (20 May 2026) | Viewed by 4745

Special Issue Editor

Dr. Myrna Gloria Candelaria

E-Mail Website
Guest Editor
Instituto Nacional de Cancerología, Mexico City, Mexico
Interests: lymphoma; non-Hodgkin lymphoma; B cell lymphoma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hematological malignancies comprise a heterogeneous group of diseases, in whom the knowledge of implicated pathways in pathogenesis has allowed advances in classification and targeted therapy.

In recent years, numerous genomic sequencing studies have primarily targeted recurrent mutations in individual genes, elucidating underlying oncogenic mechanisms. Moreover, molecular classifications have deepened our understanding of hematological diseases. Therefore, deeper and more detailed analyses using genomic, transcriptome, and epigenetic data have been performed by different research groups in order to refine the disease classification into clusters related to the disease impact and clinical outcomes.

This Special Issue will include reviews and research studies regarding the role of genomes, epigenetic regulation, genes implicated in cell cycle control, proliferation, apoptosis, biological processes participating in the pathogenesis, and the impact on treatment of patients.

I look forward to your submissions.

Dr. Myrna Gloria Candelaria
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 250 words) can be sent to the Editorial Office for assessment.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • pathogenesis
  • B-cell lymphoma regulation
  • epigenetics and hematology
  • bispecific antibodies in hematology
  • hematologic malignancies

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Published Papers (4 papers)

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Research

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17 pages, 1728 KB  
Article
Application of the New IMWG/IMS High-Risk Classification for Multiple Myeloma: Analysis of a Large Real-World Romanian Cohort
by Sorina Nicoleta Badelita, Sinziana Barbu, Onda-Tabita Calugaru, Cerasela Jardan, Codruta Delia Popa, Larisa Zidaru, Mihai Emanuel Himcinschi, Bogdan Nicolas Smadu, Iulia Ursuleac and Daniel Coriu
Int. J. Mol. Sci. 2026, 27(10), 4620; https://doi.org/10.3390/ijms27104620 - 21 May 2026
Viewed by 187
Abstract
Multiple myeloma (MM) is a biologically heterogeneous plasma cell malignancy in which prognosis is strongly influenced by cytogenetic abnormalities. Recent updates from the International Myeloma Working Group (IMWG), along with the European Hematology Association (EHA) and European Myeloma Network (EMN), have refined the [...] Read more.
Multiple myeloma (MM) is a biologically heterogeneous plasma cell malignancy in which prognosis is strongly influenced by cytogenetic abnormalities. Recent updates from the International Myeloma Working Group (IMWG), along with the European Hematology Association (EHA) and European Myeloma Network (EMN), have refined the definition of high-risk (HR) disease by integrating TP53 alterations, chromosome 1 abnormalities, and specific combinations of cytogenetic lesions. However, validation of these criteria in real-world patient populations remains limited. We conducted a retrospective, single-center study including 738 patients diagnosed with MM between 2017 and 2025, of whom 408 had available fluorescence in situ hybridization (FISH) data at diagnosis. Patients were reclassified according to the latest IMWG/IMS high-risk criteria proposed in international literature. Cytogenetic abnormalities, treatment patterns, and clinical outcomes, including overall survival (OS), progression-free survival (PFS), response rates, and relapse, were analyzed. Survival was estimated using the Kaplan–Meier method. A total of 103 patients (25%) were reclassified as high-risk according to IMWG/IMS high-risk criteria. Cytogenetic HR abnormalities were identified in 17.2% of cases, with del(17p) being the most frequent (14.7%). Median OS and PFS in HR patients were 52.4 months and 16 months, respectively, compared with 68.4 months and 28 months in standard-risk patients (log-rank test p values of 0.0197 and 0.0004, respectively). Although overall response rates were high (83% in HR vs. 91% in standard-risk), relapse remained frequent in HR patients. Outcomes varied significantly according to cytogenetic complexity. Isolated del(17p) was associated with improved survival compared with cases harboring additional abnormalities, while double-hit and triple-hit profiles demonstrated inferior outcomes. The presence of chromosome 1 abnormalities, particularly in combination with IGH translocations, further worsened prognosis. Among HR patients, 44% underwent autologous stem cell transplantation (ASCT), including 10 cases of TANDEM ASCT. No survival benefit was observed for TANDEM compared with single ASCT, with median OS of 52.9 vs. 78.3 months, respectively (log-rank test p values of 0.2516). Our real-world analysis supports the prognostic relevance of the updated IMS/IMWG high-risk criteria in MM. Cytogenetic complexity, rather than individual abnormalities alone, is a key determinant of outcome. Despite high response rates achieved with modern therapies, survival remains inferior in HR patients. TANDEM ASCT did not confer additional benefit in this cohort, supporting a more individualized approach to treatment intensification. Full article
(This article belongs to the Special Issue Hematologic Malignancies: From Molecular Pathology to Novel Therapeutics)
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11 pages, 1014 KB  
Article
Clonal Hematopoiesis and Outcomes After High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with AML, Myeloma, and Lymphoma
by Corinne Natalie Schmid, Katharina Sponagel, Ulrike Bacher, Katja Seipel, Naomi Porret, Gertrud Wiedemann, Michèle Hoffmann, Michael Daskalakis and Thomas Pabst
Int. J. Mol. Sci. 2025, 26(16), 8021; https://doi.org/10.3390/ijms26168021 - 19 Aug 2025
Cited by 1 | Viewed by 1751
Abstract
Autologous stem cell transplantation (ASCT) after high-dose chemo-therapy (HDCT) is an option of consolidation therapy in patients with AML, lymphoma, or myeloma. Clonal hematopoiesis (CH) is a premalignant state, associated with an increased risk of hematological cancer. The incidence of CH in patients [...] Read more.
Autologous stem cell transplantation (ASCT) after high-dose chemo-therapy (HDCT) is an option of consolidation therapy in patients with AML, lymphoma, or myeloma. Clonal hematopoiesis (CH) is a premalignant state, associated with an increased risk of hematological cancer. The incidence of CH in patients with AML, myeloma, and lymphoma and its effect on the outcome after HDCT/ASCT remain poorly studied. Here we screened 142 patients treated with HDCT/ASCT between 2002 and 2021 at Bern University Hospital for somatic gene mutations in ASXL1, DNMT3A, JAK2, TET2, and TP53. CH-associated somatic gene mutations were detected in 14/31 AML patients (45%), 13/64 myeloma patients (20%), and 9/47 lymphoma patients (19%). Clinical characteristics, treatment modalities, and responses to treatment were similar in patients with and without CH. Patients with CH-associated gene mutations had higher relapse rates and reduced progression free survival, most evident in lymphoma patients (p = 0.007). Overall survival tended to be shorter in lymphoma patients with CH-associated mutations (p = 0.078), whereas this was not observed in AML and myeloma patients. Survival in lymphoma patients with CH was inferior, which may have an impact on post-transplant surveillance strategies in the future. In contrast, survival outcomes were not associated significantly with CH in AML and myeloma patients in our study. Longer follow-ups and larger cohorts will be needed to validate our observations. Full article
(This article belongs to the Special Issue Hematologic Malignancies: From Molecular Pathology to Novel Therapeutics)
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Review

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20 pages, 997 KB  
Review
Decoding NOTCH1: From T-Cell Development Guardian to Driver of Pediatric T-Cell Lymphoblastic Lymphoma
by Fran Leijnen and Tim Lammens
Int. J. Mol. Sci. 2026, 27(4), 2083; https://doi.org/10.3390/ijms27042083 - 23 Feb 2026
Viewed by 1142
Abstract
T-cell lymphoblastic lymphoma (T-LBL) is an aggressive malignancy of immature T-cells accounting for a substantial proportion of pediatric non-Hodgkin lymphoma cases. Current chemotherapeutic regimens achieve five-year event-free survival rates of 80–90%, yet relapse occurs in approximately 20% of patients and remains a major [...] Read more.
T-cell lymphoblastic lymphoma (T-LBL) is an aggressive malignancy of immature T-cells accounting for a substantial proportion of pediatric non-Hodgkin lymphoma cases. Current chemotherapeutic regimens achieve five-year event-free survival rates of 80–90%, yet relapse occurs in approximately 20% of patients and remains a major therapeutic challenge. This underscores the need for improved, molecularly informed treatment strategies. Recent genomic profiling has highlighted the central role of NOTCH1 signaling in T-LBL pathogenesis. NOTCH1, a transmembrane receptor critical for T-cell differentiation and maturation, requires tightly regulated activation during normal thymocyte development. Dysregulated signaling disrupts this balance, driving aberrant proliferation and impaired differentiation, characteristics of malignant transformation. While activating mutations have long been recognized as key oncogenic events, the recent identification of recurrent NOTCH1 translocations, associated with adverse outcomes, reveals an additional mechanism of pathway activation. These findings reinforce NOTCH1 as a pivotal oncogenic hub in T-cell malignancies and a compelling target for therapeutic intervention. This review synthesizes current insights into the molecular landscape of pediatric T-LBL, with a focus on the biological and clinical implications of NOTCH1 mutations and translocations. Furthermore, we examine emerging approaches to therapeutically exploit aberrant NOTCH1 signaling for the more precise and effective treatment of this disease and formulate outstanding research questions. Full article
(This article belongs to the Special Issue Hematologic Malignancies: From Molecular Pathology to Novel Therapeutics)
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17 pages, 1398 KB  
Review
Pathways of Resistance: Modern Multiple Myeloma Therapies and Overcoming Reliance on Genomic Integrity
by Iulianna Taritsa and Eric Fossel
Int. J. Mol. Sci. 2026, 27(3), 1439; https://doi.org/10.3390/ijms27031439 - 31 Jan 2026
Viewed by 999
Abstract
Multiple myeloma (MM) is the second most common hematological malignancy in the US and Europe—comprising approximately 10% of all hematologic cancer cases—and its incidence has increased over the last three decades by approximately 120% due to an aging world population. It remains an [...] Read more.
Multiple myeloma (MM) is the second most common hematological malignancy in the US and Europe—comprising approximately 10% of all hematologic cancer cases—and its incidence has increased over the last three decades by approximately 120% due to an aging world population. It remains an incurable cancer among diseases in modern medicine. This review outlines the relevant cancer biology of MM, with a special emphasis on the role of tumor protein p53. We provide the most up-to-date summary of the current drugs in clinical or pre-clinical trials targeting weaknesses in the MM apoptotic mechanism. In addition, we highlight the potential for new routes to strike and kill myeloma cells, possibly creating a vaccine-like effect that prevents relapse, using the principles of immunogenic cell death (ICD). Full article
(This article belongs to the Special Issue Hematologic Malignancies: From Molecular Pathology to Novel Therapeutics)
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