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Special Issue "Molecular Immunology in Hematological Disorders"

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

Deadline for manuscript submissions: 28 February 2022.

Special Issue Editor

Prof. Dr. Akiyoshi Takami
E-Mail Website
Guest Editor
Department of Internal Medicine, Division of Hematology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan
Interests: hematopoietic stem cell transplantation; functional genetics; molecular immunobiology; NK cells; laboratory hematology; hematologic malignancies; natural compounds; bone marrow failures; tranfusion medicine

Special Issue Information

Dear Colleagues,

The mechanism by which hematological malignancies such as leukemia, lymphoma, and myeloma develop and proliferate in vivo is not yet fully understood. However, the possibility of eradicating cancer cells not only through allogeneic hematopoietic stem cell transplantation but also single-molecule targeted therapy, such as with CAR-T cells, suggests that the immune system, including innate and adaptive immunity, plays an important role in the development and pathophysiology of hematological malignancies. The involvement of immunological mechanisms has also been suggested in benign hematological disorders such as acquired aplastic anemia, paroxysmal nocturnal hemochromatosis, immune thrombocytopenia, thrombotic microangiopathy, and hemolytic anemia. In addition, hematological abnormalities associated with immunological dysregulation have also been noted in infectious diseases such as COVID-19 and autoimmune diseases. Therefore, there is a close pathophysiological relationship between hematological disorders and the immune system, and elucidation of these molecular mechanisms will advance the diagnosis and treatment of benign and malignant hematologic diseases, infectious diseases, and autoimmune diseases. This Special Issue focuses on molecular immunology in hematology and specifically welcomes studies that elucidate molecular immunological mechanisms in the diagnosis and treatment of hematological disorders, in addition to other topics that are relevant to the Special Issue theme.

Prof. Dr. Akiyoshi Takami
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 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

  • Anemia
  • Bioinformatics
  • COVID-19
  • Functional genetics
  • Genetically-engineered therapy
  • Hematopoietic stem cell transplantation
  • Leukemia
  • lymphoma
  • Myeloma
  • Thrombocytopenia

Published Papers (2 papers)

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Article
Synergistic Effects of Venetoclax and Daratumumab on Antibody-Dependent Cell-Mediated Natural Killer Cytotoxicity in Multiple Myeloma
Int. J. Mol. Sci. 2021, 22(19), 10761; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910761 - 05 Oct 2021
Viewed by 358
Abstract
The prognosis of multiple myeloma (MM) has drastically improved owing to the development of new drugs, such as proteasome inhibitors and immunomodulatory drugs. Nevertheless, MM is an extremely challenging disease, and many patients are still refractory to the existing therapies, thus requiring new [...] Read more.
The prognosis of multiple myeloma (MM) has drastically improved owing to the development of new drugs, such as proteasome inhibitors and immunomodulatory drugs. Nevertheless, MM is an extremely challenging disease, and many patients are still refractory to the existing therapies, thus requiring new treatment alternatives. Venetoclax is a selective, orally bioavailable inhibitor of BCL-2 that shows efficacy in MM not only as a single agent but also in combination therapy, especially for MM patients with translocation t(11;14). However, many patients are refractory to this drug. Here, we treated the MM cell lines KMS12PE and KMS27 with a combination treatment of venetoclax targeting BCL-2 and daratumumab targeting CD38 to evaluate the synergistic cytotoxicity of these drugs in vitro. MM cell lines were co-cultured with natural killer (NK) cells at an effector:target ratio of 0.3:1 in the presence of serial concentrations of daratumumab and venetoclax, and the resulting apoptotic MM cells were detected by flow cytometry using annexin V. These results indicated that the antibody-dependent cell-mediated NK cytotoxicity was enhanced in KMS12PE and KMS27 cells harboring t(11;14) with a high BCL-2 expression, suggesting that the combination treatment of venetoclax and daratumumab should be especially effective in patients with these characteristics. Full article
(This article belongs to the Special Issue Molecular Immunology in Hematological Disorders)
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Review

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Review
Neoantigen-Specific T-Cell Immune Responses: The Paradigm of NPM1-Mutated Acute Myeloid Leukemia
Int. J. Mol. Sci. 2021, 22(17), 9159; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179159 - 25 Aug 2021
Cited by 1 | Viewed by 586
Abstract
The C-terminal aminoacidic sequence from NPM1-mutated protein, absent in normal human tissues, may serve as a leukemia-specific antigen and can be considered an ideal target for NPM1-mutated acute myeloid leukemia (AML) immunotherapy. Different in silico instruments and in vitro/ex vivo immunological platforms [...] Read more.
The C-terminal aminoacidic sequence from NPM1-mutated protein, absent in normal human tissues, may serve as a leukemia-specific antigen and can be considered an ideal target for NPM1-mutated acute myeloid leukemia (AML) immunotherapy. Different in silico instruments and in vitro/ex vivo immunological platforms have identified the most immunogenic epitopes from NPM1-mutated protein. Spontaneous development of endogenous NPM1-mutated-specific cytotoxic T cells has been observed in patients, potentially contributing to remission maintenance and prolonged survival. Genetically engineered T cells, namely CAR-T or TCR-transduced T cells, directed against NPM1-mutated peptides bound to HLA could prospectively represent a promising therapeutic approach. Although either adoptive or vaccine-based immunotherapies are unlikely to be highly effective in patients with full-blown leukemia, these strategies, potentially in combination with immune-checkpoint inhibitors, could be promising in maintaining remission or preemptively eradicating persistent measurable residual disease, mainly in patients ineligible for allogeneic hematopoietic stem cell transplant (HSCT). Alternatively, neoantigen-specific donor lymphocyte infusion derived from healthy donors and targeting NPM1-mutated protein to selectively elicit graft-versus-leukemia effect may represent an attractive option in subjects experiencing post-HSCT relapse. Future studies are warranted to further investigate dynamics of NPM1-mutated-specific immunity and explore whether novel individualized immunotherapies may have potential clinical utility in NPM1-mutated AML patients. Full article
(This article belongs to the Special Issue Molecular Immunology in Hematological Disorders)
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