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Biomedicines
Special Issues
Recent Advances in Myelodysplastic/Myeloproliferative Neoplasms
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Recent Advances in Myelodysplastic/Myeloproliferative Neoplasms

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

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 13686

Special Issue Editor

Dr. Marko Lucijanić

E-Mail Website
Guest Editor
1. Department of Hematology, University Hospital Dubrava, 10000 Zagreb, Croatia
2. School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Interests: thrombocythemia; primary myelofibrosis; polycythemia vera erythrocyte indices; mean platelet volume; megakaryocyte; COVID; vaccination; spleen biology

Special Issue Information

Dear Colleagues,

The rapidly developing area of BCR-ABL negative chronic myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) is profoundly affected by novel therapeutic and conceptual advances, as well as by the COVID-19 pandemic. In addition to the progressive nature of these entities and the risk for leukemic transformation and death due to bone marrow failure, these patients experience high cardiovascular disease burden and substantial risks of thrombosis and bleeding. Other aspects of these diseases, such as chronic renal disease and autoimmune disorders, as well as the mutual relationship with chronic systemic inflammation and cancer, are also emerging, implying that these patients might represent the human model for inflammation and cancer.

The aim of this special issue is to collect articles that investigate novel and contemporary issues in the context of MPN and MDS. Manuscripts covering all aspects of research related to MPN and MDS as well as review articles focused on important novel topics are welcome.

Dr. Marko Lucijanić
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.

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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 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.

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Published Papers (5 papers)

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Research

16 pages, 1454 KiB  
Article
Identifying Patients with Polycythemia Vera at Risk of Thrombosis after Hydroxyurea Initiation: The Polycythemia Vera—Advanced Integrated Models (PV-AIM) Project
by Srdan Verstovsek, Ivan Krečak, Florian H. Heidel, Valerio De Stefano, Kenneth Bryan, Mike W. Zuurman, Michael Zaiac, Mara Morelli, Aoife Smyth, Santiago Redondo, Erwan Bigan, Michael Ruhl, Christoph Meier, Magali Beffy and Jean-Jacques Kiladjian
Biomedicines 2023, 11(7), 1925; https://doi.org/10.3390/biomedicines11071925 - 7 Jul 2023
Cited by 11 | Viewed by 3224
Abstract
Patients with polycythemia vera (PV) are at significant risk of thromboembolic events (TE). The PV-AIM study used the Optum® de-identified Electronic Health Record dataset and machine learning to identify markers of TE in a real-world population. Data for 82,960 patients with PV [...] Read more.
Patients with polycythemia vera (PV) are at significant risk of thromboembolic events (TE). The PV-AIM study used the Optum® de-identified Electronic Health Record dataset and machine learning to identify markers of TE in a real-world population. Data for 82,960 patients with PV were extracted: 3852 patients were treated with hydroxyurea (HU) only, while 130 patients were treated with HU and then changed to ruxolitinib (HU-ruxolitinib). For HU-alone patients, the annualized incidence rates (IR; per 100 patients) decreased from 8.7 (before HU) to 5.6 (during HU) but increased markedly to 10.5 (continuing HU). Whereas for HU-ruxolitinib patients, the IR decreased from 10.8 (before HU) to 8.4 (during HU) and was maintained at 8.3 (after switching to ruxolitinib). To better understand markers associated with TE risk, we built a machine-learning model for HU-alone patients and validated it using an independent dataset. The model identified lymphocyte percentage (LYP), neutrophil percentage (NEP), and red cell distribution width (RDW) as key markers of TE risk, and optimal thresholds for these markers were established, from which a decision tree was derived. Using these widely used laboratory markers, the decision tree could be used to identify patients at high risk for TE, facilitate treatment decisions, and optimize patient management. Full article
(This article belongs to the Special Issue Recent Advances in Myelodysplastic/Myeloproliferative Neoplasms)
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16 pages, 13437 KiB  
Article
Polypharmacy, Potentially Inappropriate Medications, and Drug-to-Drug Interactions in Patients with Chronic Myeloproliferative Neoplasms
by Ivan Krečak, Ljerka Pivac, Marko Lucijanić and Marko Skelin
Biomedicines 2023, 11(5), 1301; https://doi.org/10.3390/biomedicines11051301 - 27 Apr 2023
Cited by 6 | Viewed by 2066
Abstract
Polypharmacy, potentially inappropriate medications (PIMs), and drug-to-drug interactions (DDIs) are highly prevalent in the elderly and may have adverse effects on health-related outcomes. Their occurrence and clinical and prognostic associations in patients with chronic myeloproliferative neoplasms (MPN) are unknown. We retrospectively evaluated polypharmacy, [...] Read more.
Polypharmacy, potentially inappropriate medications (PIMs), and drug-to-drug interactions (DDIs) are highly prevalent in the elderly and may have adverse effects on health-related outcomes. Their occurrence and clinical and prognostic associations in patients with chronic myeloproliferative neoplasms (MPN) are unknown. We retrospectively evaluated polypharmacy, PIMs, and DDIs in a cohort of 124 MPN patients (essential thrombocythemia, ET = 63, polycythemia vera, PV = 44, myelofibrosis = 9, MPN unclassifiable = 8) from a single community hematology practice. There were 761 drug prescriptions with a median of five prescribed medications per patient. Polypharmacy, at least one PIM (calculated for persons >60 years of age, n = 101), and at least one DDI were recorded in 76 (61.3%), 46 (45.5%), and 77 (62.1%) of patients, respectively. Seventy-four (59.6%) and twenty-one (16.9%) patients had at least one C or at least one D interaction, respectively. Among other associations, polypharmacy and DDIs were associated with older age, management of disease-related symptoms, osteoarthritis/osteoporosis, and different CV disorders. In multivariate analyses adjusted for clinically meaningful parameters, both polypharmacy and DDIs were significantly associated with inferior overall survival (OS) and time to thrombosis (TTT), whereas PIMs had no significant associations with neither OS nor TTT. There were no associations with bleeding or transformation risks. Polypharmacy, DDIs, and PIMs are very frequent among MPN patients and may have important clinical associations. Full article
(This article belongs to the Special Issue Recent Advances in Myelodysplastic/Myeloproliferative Neoplasms)
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11 pages, 602 KiB  
Article
Non-Myelofibrosis Chronic Myeloproliferative Neoplasm Patients Show Better Seroconversion Rates after SARS-CoV-2 Vaccination Compared to Other Hematologic Diseases: A Multicentric Prospective Study of KroHem
by Zrinka Sertić, Marko Lucijanić, Sandra Bašić-Kinda, Ranka Serventi Seiwerth, Vlatka Periša, Dubravka Sertić, Božena Coha, Dražen Pulanić, Zinaida Perić, Lana Desnica, Mirta Mikulić, Marijo Vodanović, Ivo Radman-Livaja, Dragana Šegulja, Dunja Rogić, Toni Valković, Igor Aurer and Nadira Duraković
Biomedicines 2022, 10(11), 2892; https://doi.org/10.3390/biomedicines10112892 - 11 Nov 2022
Cited by 4 | Viewed by 2249
Abstract
Disease- and treatment-mediated immunodeficiency might render SARS-CoV-2 vaccines less effective in patients with hematologic diseases. We performed a prospective non-interventional study to evaluate humoral response after one and two doses of mRNA-1273, BNT162b2, or ChAdOx1 nCoV-19 vaccine in 118 patients with different malignant [...] Read more.
Disease- and treatment-mediated immunodeficiency might render SARS-CoV-2 vaccines less effective in patients with hematologic diseases. We performed a prospective non-interventional study to evaluate humoral response after one and two doses of mRNA-1273, BNT162b2, or ChAdOx1 nCoV-19 vaccine in 118 patients with different malignant or non-malignant hematologic diseases from three Croatian treatment centers. An electrochemiluminescent assay was used to measure total anti-SARS-CoV-2 S-RBD antibody titers. After one vaccine dose, 20/66 (33%) achieved seropositivity with a median antibody titer of 6.1 U/mL. The response rate (58/90, 64.4%) and median antibody titer (>250 U/mL) were higher after two doses. Seropositivity varied with diagnosis (overall p < 0.001), with the lowest rates in lymphoma (34.6%) and chronic lymphocytic leukemia (52.5%). The overall response rate in chronic myeloproliferative neoplasms (CMPN) was 81.3% but reached 100% in chronic myeloid leukemia and other non-myelofibrosis CMPN. At univariable analysis, age > 67 years, non-Hodgkin’s lymphoma, active treatment, and anti-CD20 monoclonal antibody therapy increased the likelihood of no vaccine response, while hematopoietic stem cell recipients were more likely to respond. Age and anti-CD20 monoclonal antibody therapy remained associated with no response in a multivariable model. Patients with the hematologic disease have attenuated responses to SARS-CoV-2 vaccines, and significant variations in different disease subgroups warrant an individualized approach. Full article
(This article belongs to the Special Issue Recent Advances in Myelodysplastic/Myeloproliferative Neoplasms)
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14 pages, 2651 KiB  
Article
Antitumor Effect of Brusatol in Acute Lymphoblastic Leukemia Models Is Triggered by Reactive Oxygen Species Accumulation
by Joana Jorge, Nisa Magalhães, Raquel Alves, Beatriz Lapa, Ana Cristina Gonçalves and Ana Bela Sarmento-Ribeiro
Biomedicines 2022, 10(9), 2207; https://doi.org/10.3390/biomedicines10092207 - 6 Sep 2022
Cited by 5 | Viewed by 2168
Abstract
Acute lymphoblastic leukemia (ALL) is one of the most common hematological malignancies at pediatric ages and is characterized by different chromosomal rearrangements and genetic abnormalities involved in the differentiation and proliferation of lymphoid precursor cells. Brusatol is a quassinoid plant extract extensively studied [...] Read more.
Acute lymphoblastic leukemia (ALL) is one of the most common hematological malignancies at pediatric ages and is characterized by different chromosomal rearrangements and genetic abnormalities involved in the differentiation and proliferation of lymphoid precursor cells. Brusatol is a quassinoid plant extract extensively studied due to its antineoplastic effect through global protein synthesis and nuclear factor erythroid 2-related factor-2 (NRF2) signaling inhibition. NRF2 is the main regulator of cellular antioxidant response and reactive oxygen species (ROS), which plays an important role in oxidative stress regulation. This study aimed to evaluate the effect of brusatol in in vitro models of ALL. KOPN-8 (B-ALL), CEM (T-ALL), and MOLT-4 (T-ALL) cell lines were incubated with increasing concentrations of brusatol, and the metabolic activity was evaluated using the resazurin assay. Flow cytometry was used to evaluate cell death, cell cycle, mitochondrial membrane potential (Δψmit), and to measure ROS and reduced glutathione (GSH) levels. Our results show that brusatol promoted a decrease in metabolic activity in ALL cell lines in a time-, dose-, and cell-line-dependent manner. Brusatol induced a cytostatic effect by cell cycle arrest in G0/G1 in all cell lines; however, cell death mediated by apoptosis was only observed in T-ALL cells. Brusatol leads to an oxidative stress imbalance by the increase in ROS levels, namely, superoxide anion. Redox imbalance and cellular apoptosis induced by brusatol are highly modulated by mitochondria disruption as a decrease in mitochondrial membrane potential is detected. These data suggest that brusatol might represent a new therapeutic approach for acute lymphoblastic leukemia, particularly for ALL T-cell lineage. Full article
(This article belongs to the Special Issue Recent Advances in Myelodysplastic/Myeloproliferative Neoplasms)
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13 pages, 2256 KiB  
Article
Combination of Elacridar with Imatinib Modulates Resistance Associated with Drug Efflux Transporters in Chronic Myeloid Leukemia
by Raquel Alves, Ana Cristina Gonçalves, Joana Jorge, António M. Almeida and Ana Bela Sarmento-Ribeiro
Biomedicines 2022, 10(5), 1158; https://doi.org/10.3390/biomedicines10051158 - 17 May 2022
Cited by 10 | Viewed by 2691
Abstract
Multidrug resistance (MDR) development has emerged as a complication that compromises the success of several chemotherapeutic agents. In chronic myeloid leukemia (CML), imatinib resistance has been associated with changes in BCR-ABL1 and intracellular drug concentration, controlled by SLC and ABC transporters. We evaluate [...] Read more.
Multidrug resistance (MDR) development has emerged as a complication that compromises the success of several chemotherapeutic agents. In chronic myeloid leukemia (CML), imatinib resistance has been associated with changes in BCR-ABL1 and intracellular drug concentration, controlled by SLC and ABC transporters. We evaluate the therapeutic potential of a P-glycoprotein and BCRP inhibitor, elacridar, in sensitive (K562 and LAMA-84) and imatinib-resistant (K562-RC and K562-RD) CML cell lines as monotherapy and combined with imatinib. Cell viability was analyzed by resazurin assay. Drug transporter activity, cell death, cell proliferation rate, and cell cycle distribution were analyzed by flow cytometry. Both resistant models presented an increased activity of BCRP and P-gP compared to K562 cells. Elacridar as monotherapy did not reach IC50 in any CML models but activated apoptosis without cytostatic effect. Nevertheless, the association of elacridar (250 nM) with imatinib overcomes resistance, re-sensitizing K562-RC and K562-RD cells with five and ten times lower imatinib concentrations, respectively. Drug combination induced apoptosis with increased cleaved-caspases-3, cleaved-PARP and DNA damage, reduced cell proliferation rate, and arrested CML cells in the S phase. These data suggest that elacridar combined with imatinib might represent a new therapeutic option for overcoming TKI resistance involving efflux transporters. Full article
(This article belongs to the Special Issue Recent Advances in Myelodysplastic/Myeloproliferative Neoplasms)
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