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Medicina
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Acute Myeloid Leukemia: Update on Diagnosis, Therapy, and Monitoring
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Acute Myeloid Leukemia: Update on Diagnosis, Therapy, and Monitoring

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 3183

Special Issue Editors

Prof. Dr. Ana Vidović

E-Mail Website
Guest Editor
1. Medical Faculty, University of Belgrade, Belgrade, Serbia
2. Clinic of Hematology, University Clinical Centre of Serbia, Belgrade, Serbia
Interests: leukemia
Prof. Dr. Andrija Bogdanović

E-Mail Website
Guest Editor
1. Medical Faculty, University of Belgrade, Belgrade, Serbia
2. Clinic of Hematology, University Clinical Centre of Serbia, Belgrade, Serbia
Interests: diagnosis of hematological malignancies; cytomorphology; symyelodysplasticum; myeloproliferative neoplasms
Dr. Nada Kraguljac

E-Mail Website
Guest Editor
Clinical Center of Serbia, Clinic of Hematology, Diagnostic Department, Laboratory for Immunophenotyping and Flow Cytometry, Belgrade, Serbia
Interests: leukemia; hematological malignancies; hematologic diseases; multiple myeloma; flow cytometry; pathology; immunology; t lymphocytes; lymphoma; autoimmunity

Special Issue Information

Dear Colleagues,

Acute myeloid leukemia (AML) is a clonal disease that occurs due to a block in the maturation of stem cells of the myeloid lineage, their enormous proliferation, as well as suppression of apoptosis. The most common cause is the activation or inactivation of certain genes, due to various cytogenetic/molecular changes, usually chromosomal translocations, deletions or some other genetic or epigenetic disorders. The incidence of AML ranges from 3.7 to 4.3 per 100,000 population per year.

Complete diagnosis of AML includes morphological/cytochemical/immunophenotypic and cytogenetic/molecular definition of the disease, according to the recommendations of the ELN working group, 2022. The most important prognostic parameter in AML is cytogenetic/molecular findings.

Intensive therapy is reserved for patients under the age of 65, without comorbidities and includes chemotherapy, allogeneic bone marrow transplantation, depending on disease markers and targeted therapy.

Due to advanced age, other comorbidities, as well as a higher frequency of unfavorable cytogenetic characteristics, elderly patients are often not suitable for intensive treatment. In them, chemotherapy is applied in reduced doses, as well as an inhibitor of the antiapoptotic bcl-2 protein along with hypomethylating agents.

Prof. Dr. Ana Vidović
Prof. Dr. Andrija Bogdanović
Dr. Nada Kraguljac
Guest Editors

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. Medicina 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 2200 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

  • acute myeloblastic leukemia
  • diagnosis
  • prognosis
  • intensive chemotherapy
  • allogeneic stem cell transplantation

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Published Papers (2 papers)

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Research

19 pages, 2205 KiB  
Article
An Ultra-Fast Validated Green UPLC-MS/MS Approach for Assessing Revumenib in Human Liver Microsomes: In Vitro Absorption, Distribution, Metabolism, and Excretion and Metabolic Stability Evaluation
by Mohamed W. Attwa, Ali S. Abdelhameed and Adnan A. Kadi
Medicina 2024, 60(12), 1914; https://doi.org/10.3390/medicina60121914 - 21 Nov 2024
Cited by 3 | Viewed by 1156
Abstract
Background and Objectives: Revumenib (SNDX-5613) is a powerful and specific inhibitor of the menin–KMT2A binding interaction. It is a small molecule that is currently being researched to treat KMT2A-rearranged (KMT2Ar) acute leukemias. Revumenib (RVB) has received Orphan Drug Designation from the US FDA [...] Read more.
Background and Objectives: Revumenib (SNDX-5613) is a powerful and specific inhibitor of the menin–KMT2A binding interaction. It is a small molecule that is currently being researched to treat KMT2A-rearranged (KMT2Ar) acute leukemias. Revumenib (RVB) has received Orphan Drug Designation from the US FDA for treating patients with AML. It has also been granted Fast Track designation by the FDA for treating pediatric and adult patients with R/R acute leukemias that have a KMT2Ar or NPM1 mutation. Materials and Methods: The target of this research was to create a fast, precise, green, and extremely sensitive UPLC-MS/MS technique for the estimation of the RVB level in human liver microsomes (HLMs), employing an ESI source. The validation procedures were carried out in accordance with the bioanalytical technique validation requirements established by the US Food and Drug Administration that involve linearity, selectivity, precision, accuracy, stability, matrix effect, and extraction recovery. The outcome data of the validation features of the UPLC-MS/MS approach were acceptable according to FDA guidelines. RVB parent ions were formed in the positive ESI source and its two fragment ions were estimated employing multiple reaction monitoring (MRM) mode. The separation of RVB and encorafenib was achieved using a C8 column (2.1 mm, 50 mm, and 3.5 µm) and isocratic mobile phase. Results: The RVB calibration curve linearity ranged from 1 to 3000 ng/mL (y = 0.6515x − 0.5459 and R2 = 0.9945). The inter-day precision and accuracy spanned from −0.23% to 11.33%, while the intra-day precision and accuracy spanned from −0.88% to 11.67%, verifying the reproducibility of the UPLC-MS/MS analytical technique. The sensitivity of the developed methodology demonstrated its capability to quantify RVB levels at an LOQ of 0.96 ng/mL. The AGREE score was 0.77, confirming the greenness of the current method. The low in vitro t1/2 (14.93 min) and high intrinsic clearance (54.31 mL/min/kg) of RVB revealed that RVB shares similarities with medications that have a high extraction ratio. Conclusions: The present LC-MS/MS approach is considered the first analytical approach with the application of metabolic stability assessment for RVB estimation in HLMs. These methods are essential for advancing the development of new pharmaceuticals, particularly in enhancing metabolic stability. Full article
(This article belongs to the Special Issue Acute Myeloid Leukemia: Update on Diagnosis, Therapy, and Monitoring)
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11 pages, 1141 KiB  
Article
Early Prediction and Streamline of Nucleophosmin Mutation Status in Acute Myeloid Leukemia Using Cup-Like Nuclear Morphology
by Ljubomir Jakovic, Vesna Djordjevic, Nada Kraguljac Kurtovic, Marijana Virijevic, Mirjana Mitrovic, Lazar Trajkovic, Ana Vidovic and Andrija Bogdanovic
Medicina 2024, 60(9), 1443; https://doi.org/10.3390/medicina60091443 - 4 Sep 2024
Viewed by 1325
Abstract
Background and Objectives: With the advent of novel therapies for nucleophosmin gene (NPM1)-mutated acute myeloid leukemia (AML), there is a growing need for the reliable prediction of NPM1 mutations. This study explored the role of cytomorphological features in the early [...] Read more.
Background and Objectives: With the advent of novel therapies for nucleophosmin gene (NPM1)-mutated acute myeloid leukemia (AML), there is a growing need for the reliable prediction of NPM1 mutations. This study explored the role of cytomorphological features in the early prediction of NPM1-mutated AML. Materials and Methods: Altogether, 212 de novo AML cases with normal karyotypes, diagnosed and treated at a single institution within 5 years (2018–2023), were retrospectively evaluated. A final diagnosis of NPM1-mutated AML, based on the World Health Organization (WHO) integrated criteria, including real-time based identification of NPM1 mutation and normal karyotype, was established in 83/212 (39.15%) cases. Results: Cup-like blasts (CLBs), a cytomorphological feature suggestive of NPM1-mutated AML, were detected in 56/83 (67%) patients. Most cases (44/56, 78.6%) had CLB ≥ 10%. In total, 27 of 83 AML NPM1-mutated patients had no CLB morphology (missed call). Additionally, two of 212 had CLB morphology without confirmed NPM1 mutation (wrong call). The positive/negative predictive values of cytomorphological evaluation for CLB ≥ 10% were 95.7%/75.6%, with sensitivity/specificity of 53%/98.5%, while the accuracy was 80.7%. We noted an increased percentage of CLBs (≥15%) in 77.8% and 50% of patients with AML without and with granulocytic maturation, respectively (the specificity for NPM1 mutation prediction was 100%). CLB was associated with fms-like tyrosine kinase 3 (FLT3) mutation (p = 0.03), but, without statistical significance for CLB ≥ 10% and CLB ≥ 15%. Conclusions: Our investigation confirmed that the morphological identification of CLB at diagnosis represents a reliable and easily reproducible tool for the early prediction of NPM1 mutations, enabling a streamlined genetic work-up for its confirmation. This may facilitate considering the early administration of individualized therapies by clinicians for specific patients. Full article
(This article belongs to the Special Issue Acute Myeloid Leukemia: Update on Diagnosis, Therapy, and Monitoring)
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