ijms-logo

Journal Browser

Journal Browser

Molecular Aspects of Hematological Malignancies and Benign Hematological Disorders 2.0

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

Deadline for manuscript submissions: 25 May 2024 | Viewed by 9289

Special Issue Editor


E-Mail Website
Guest Editor
1. Department of Pathophysiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
2. Clinic of Hematology, Filantropia City Hospital, 200143 Craiova, Romania
Interests: hematology; internal medicine; pathophysiology; modern methods of teaching
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hematological malignancies are complex disorders characterized by a complex molecular basis. The study and current understanding of their pathogenesis has been made possible by the recents advances in laboratory techniques such as molecular biology, flow-cytometry, cytogenetics, pathology and immunohistochemistry (to name a few), all of which have enabled the discovery and implementation of targeted therapies in the management of these peculiar disorders. The current special issue aims to provide an insight into the molecular aspects of blood cancers as well as their impact on the diagnosis, evolution and management of hematological malignancies. The submission of preclinical and translational research articles, as well as narrative and systematic reviews, is greatly encouraged.

Prof. Dr. Amelia Maria Găman
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. 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

  • myeloproliferative neoplasms
  • leukemia
  • lymphoma
  • multiple myeloma
  • oxidative stress
  • inflammation
  • microbiome
  • genetics
  • molecular biology

Published Papers (6 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Other

11 pages, 3168 KiB  
Article
Immunophenotypic but Not Genetic Changes Reclassify the Majority of Relapsed/Refractory Pediatric Cases of Early T-Cell Precursor Acute Lymphoblastic Leukemia
by Irina Demina, Aya Dagestani, Aleksandra Borkovskaia, Alexandra Semchenkova, Olga Soldatkina, Svetlana Kashpor, Yulia Olshanskaya, Julia Roumiantseva, Alexander Karachunskiy, Galina Novichkova, Michael Maschan, Elena Zerkalenkova and Alexander Popov
Int. J. Mol. Sci. 2024, 25(11), 5610; https://doi.org/10.3390/ijms25115610 - 21 May 2024
Viewed by 237
Abstract
Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) develops from very early cells with the potential for both T-cell and myeloid differentiation. The ambiguous nature of leukemic blasts in ETP-ALL may lead to immunophenotypic alterations at relapse. Here, we address immunophenotypic alterations and related [...] Read more.
Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) develops from very early cells with the potential for both T-cell and myeloid differentiation. The ambiguous nature of leukemic blasts in ETP-ALL may lead to immunophenotypic alterations at relapse. Here, we address immunophenotypic alterations and related classification issues, as well as genetic features of relapsed pediatric ETP-ALL. Between 2017 and 2022, 7518 patients were diagnosed with acute leukemia (AL). In addition to conventional immunophenotyping, karyotyping, and FISH studies, we performed next-generation sequencing of the T-cell receptor clonal repertoire and reverse transcription PCR and RNA sequencing for patients with ETP-ALL at both initial diagnosis and relapse. Among a total of 534 patients diagnosed with T-cell ALL (7.1%), 60 had ETP-ALL (11.2%). Ten patients with ETP-ALL experienced relapse or progression on therapy (16.7%), with a median time to event of 5 months (ranging from two weeks to 5 years). Most relapses were classified as AL of ambiguous lineage (n = 5) and acute myeloid leukemia (AML) (n = 4). Major genetic markers of leukemic cells remained unchanged at relapse. Of the patients with relapse, four had polyclonal leukemic populations and a relapse with AML or bilineal mixed-phenotype AL (MPAL). Three patients had clonal TRD rearrangements and relapse with AML, undifferentiated AL, or retention of the ETP-ALL phenotype. ETP-ALL relapse requires careful clinical and laboratory diagnosis. Treatment decisions should rely mainly on initial examination data, taking into account both immunophenotypic and molecular/genetic characteristics. Full article
Show Figures

Figure 1

20 pages, 10966 KiB  
Article
Unusual Presentation of SET::NUP214-Associated Concomitant Hematological Neoplasm in a Child—Diagnostic and Treatment Struggle
by Yaroslav Menchits, Tatiana Salimova, Alexander Komkov, Dmitry Abramov, Tatiana Konyukhova, Ruslan Abasov, Elena Raykina, Albert Itov, Marina Gaskova, Aleksandra Borkovskaia, Anna Kazakova, Olga Soldatkina, Svetlana Kashpor, Alexandra Semchenkova, Alexander Popov, Galina Novichkova, Yulia Olshanskaya, Alexey Maschan and Elena Zerkalenkova
Int. J. Mol. Sci. 2023, 24(19), 14451; https://doi.org/10.3390/ijms241914451 - 22 Sep 2023
Viewed by 1277
Abstract
Simultaneous multilineage hematologic malignancies are uncommon and associated with poorer prognosis than single-lineage leukemia or lymphoma. Here, we describe a concomitant malignant neoplasm in a 4-year-old boy. The child presented with massive lymphoproliferative syndrome, nasal breathing difficulties, and snoring. Morphological, immunocytochemical, and flow [...] Read more.
Simultaneous multilineage hematologic malignancies are uncommon and associated with poorer prognosis than single-lineage leukemia or lymphoma. Here, we describe a concomitant malignant neoplasm in a 4-year-old boy. The child presented with massive lymphoproliferative syndrome, nasal breathing difficulties, and snoring. Morphological, immunocytochemical, and flow cytometry diagnostics showed coexistence of acute myeloid leukemia (AML) and peripheral T-cell lymphoma (PTCL). Molecular examination revealed a rare t(9;9)(q34;q34)/SET::NUP214 translocation as well as common TCR clonal rearrangements in both the bone marrow and lymph nodes. The disease showed primary refractoriness to both lymphoid and myeloid high-dose chemotherapy as well as combined targeted therapy (trametinib + ruxolitinib). Hence, HSCT was performed, and the patient has since been in complete remission for over a year. This observation highlights the importance of molecular techniques for determining the united nature of complex SET::NUP214-positive malignant neoplasms arising from precursor cells with high lineage plasticity. Full article
Show Figures

Figure 1

22 pages, 4168 KiB  
Article
Defining the Basal and Immunomodulatory Mediator-Induced Phosphoprotein Signature in Pediatric B Cell Acute Lymphoblastic Leukemia (B-ALL) Diagnostic Samples
by Aaruni Khanolkar, Guorong Liu and Bridget M. Simpson Schneider
Int. J. Mol. Sci. 2023, 24(18), 13937; https://doi.org/10.3390/ijms241813937 - 11 Sep 2023
Viewed by 837
Abstract
It is theorized that dysregulated immune responses to infectious insults contribute to the development of pediatric B-ALL. In this context, our understanding of the immunomodulatory-mediator-induced signaling responses of leukemic blasts in pediatric B-ALL diagnostic samples is rather limited. Hence, in this study, we [...] Read more.
It is theorized that dysregulated immune responses to infectious insults contribute to the development of pediatric B-ALL. In this context, our understanding of the immunomodulatory-mediator-induced signaling responses of leukemic blasts in pediatric B-ALL diagnostic samples is rather limited. Hence, in this study, we defined the signaling landscape of leukemic blasts, as well as normal mature B cells and T cells residing in diagnostic samples from 63 pediatric B-ALL patients. These samples were interrogated with a range of immunomodulatory-mediators within 24 h of collection, and phosflow analyses of downstream proximal signaling nodes were performed. Our data reveal evidence of basal hyperphosphorylation across a broad swath of these signaling nodes in leukemic blasts in contrast to normal mature B cells and T cells in the same sample. We also detected similarities in the phosphoprotein signature between blasts and mature B cells in response to IFNγ and IL-2 treatment, but significant divergence in the phosphoprotein signature was observed between blasts and mature B cells in response to IL-4, IL-7, IL-10, IL-21 and CD40 ligand treatment. Our results demonstrate the existence of both symmetry and asymmetry in the phosphoprotein signature between leukemic and non-leukemic cells in pediatric B-ALL diagnostic samples. Full article
Show Figures

Figure 1

25 pages, 3484 KiB  
Article
Transcriptome Analysis of Diffuse Large B-Cell Lymphoma Cells Inducibly Expressing MyD88 L265P Mutation Identifies Upregulated CD44, LGALS3, NFKBIZ, and BATF as Downstream Targets of Oncogenic NF-κB Signaling
by Marcello Turi, Anjana Anilkumar Sithara, Lucie Hofmanová, David Žihala, Dhwani Radhakrishnan, Alexander Vdovin, Sofija Knápková, Tereza Ševčíková, Zuzana Chyra, Tomáš Jelínek, Michal Šimíček, Annamaria Gullà, Kenneth Carl Anderson, Roman Hájek and Matouš Hrdinka
Int. J. Mol. Sci. 2023, 24(6), 5623; https://doi.org/10.3390/ijms24065623 - 15 Mar 2023
Cited by 6 | Viewed by 3417
Abstract
During innate immune responses, myeloid differentiation primary response 88 (MyD88) functions as a critical signaling adaptor protein integrating stimuli from toll-like receptors (TLR) and the interleukin-1 receptor (IL-1R) family and translates them into specific cellular outcomes. In B cells, somatic mutations in MyD88 [...] Read more.
During innate immune responses, myeloid differentiation primary response 88 (MyD88) functions as a critical signaling adaptor protein integrating stimuli from toll-like receptors (TLR) and the interleukin-1 receptor (IL-1R) family and translates them into specific cellular outcomes. In B cells, somatic mutations in MyD88 trigger oncogenic NF-κB signaling independent of receptor stimulation, which leads to the development of B-cell malignancies. However, the exact molecular mechanisms and downstream signaling targets remain unresolved. We established an inducible system to introduce MyD88 to lymphoma cell lines and performed transcriptomic analysis (RNA-seq) to identify genes differentially expressed by MyD88 bearing the L265P oncogenic mutation. We show that MyD88L265P activates NF-κB signaling and upregulates genes that might contribute to lymphomagenesis, including CD44, LGALS3 (coding Galectin-3), NFKBIZ (coding IkBƺ), and BATF. Moreover, we demonstrate that CD44 can serve as a marker of the activated B-cell (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) and that CD44 expression is correlated with overall survival in DLBCL patients. Our results shed new light on the downstream outcomes of MyD88L265P oncogenic signaling that might be involved in cellular transformation and provide novel therapeutical targets. Full article
Show Figures

Figure 1

14 pages, 1528 KiB  
Article
Differential Expression of LLT1, SLAM Receptors CS1 and 2B4 and NCR Receptors NKp46 and NKp30 in Pediatric Acute Lymphoblastic Leukemia (ALL)
by Sheila B. Powers, Nourhan G. Ahmed, Roslin Jose, Marissa Brezgiel, Subhash Aryal, W. Paul Bowman, Porunelloor A. Mathew and Stephen O. Mathew
Int. J. Mol. Sci. 2023, 24(4), 3860; https://doi.org/10.3390/ijms24043860 - 15 Feb 2023
Viewed by 2057
Abstract
Acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer. Most patients (85%) develop B-cell ALL; however, T-cell ALL tends to be more aggressive. We have previously identified 2B4 (SLAMF4), CS1 (SLAMF7) and LLT1 (CLEC2D) that can activate or inhibit NK cells upon [...] Read more.
Acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer. Most patients (85%) develop B-cell ALL; however, T-cell ALL tends to be more aggressive. We have previously identified 2B4 (SLAMF4), CS1 (SLAMF7) and LLT1 (CLEC2D) that can activate or inhibit NK cells upon the interaction with their ligands. In this study, the expression of 2B4, CS1, LLT1, NKp30 and NKp46 was determined. The expression profiles of these immune receptors were analyzed in the peripheral blood mononuclear cells of B-ALL and T-ALL subjects by single-cell RNA sequencing data obtained from the St. Jude PeCan data portal that showed increased expression of LLT1 in B-ALL and T-ALL subjects. Whole blood was collected from 42 pediatric ALL subjects at diagnosis and post-induction chemotherapy and 20 healthy subjects, and expression was determined at the mRNA and cell surface protein level. A significant increase in cell surface LLT1 expression in T cells, monocytes and NK cells was observed. Increased expression of CS1 and NKp46 was observed on monocytes of ALL subjects at diagnosis. A decrease of LLT1, 2B4, CS1 and NKp46 on T cells of ALL subjects was also observed post-induction chemotherapy. Furthermore, mRNA data showed altered expression of receptors in ALL subjects pre- and post-induction chemotherapy treatment. The results indicate that the differential expression of the receptors/ligand may play a role in the T-cell- and NK-cell-mediated immune surveillance of pediatric ALL. Full article
Show Figures

Figure 1

Other

Jump to: Research

9 pages, 3269 KiB  
Case Report
Germline CSF3R Variant in Chronic Myelomonocytic Leukemia: Linking Genetic Predisposition to Uncommon Hemorrhagic Symptoms
by Maria Teresa Bochicchio, Giorgia Micucci, Silvia Asioli, Martina Ghetti, Giorgia Simonetti and Alessandro Lucchesi
Int. J. Mol. Sci. 2023, 24(22), 16021; https://doi.org/10.3390/ijms242216021 - 7 Nov 2023
Viewed by 810
Abstract
Chronic myelomonocytic leukemia (CMML) is a hematological neoplasm characterized by monocytosis, splenomegaly, thrombocytopenia, and anemia. Moreover, it is associated with SRSF2 mutations and, rarely, with CSF3R variants. We present the case of an 84-year-old patient with persistent anemia and monocytosis. Due to the [...] Read more.
Chronic myelomonocytic leukemia (CMML) is a hematological neoplasm characterized by monocytosis, splenomegaly, thrombocytopenia, and anemia. Moreover, it is associated with SRSF2 mutations and, rarely, with CSF3R variants. We present the case of an 84-year-old patient with persistent anemia and monocytosis. Due to the presence of dysmorphic granulocytes, monocyte atypia, and myeloid precursors in the peripheral blood cells, the patient was subjected to a bone marrow examination. The diagnosis was consistent with CMML type 2. The Hemocoagulative test showed an increase in fibrinolysis markers. Next-generation targeted sequencing showed TET2 and SRSF2 mutations, along with an unexpected CSF3R germline missense variant, rarely encountered in CMML. The patient started Azacitidine treatment and achieved normal hemostatic process values. In conclusion, we identified a heterozygous germline mutation that, together with TET2 and SRSF2 variants, was responsible for the hemorrhagic manifestation. Full article
Show Figures

Figure 1

Back to TopTop