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Cancers
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Acute Myeloid Leukemia in Adults
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Acute Myeloid Leukemia in Adults

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: closed (30 April 2025) | Viewed by 9199

Special Issue Editor

Dr. Theodoros Karantanos

E-Mail Website
Guest Editor
Department of Oncology, Johns Hopkins University, Baltimore, MD 21218, USA
Interests: acute myeloid leukemia; myelodysplastic syndrome; myeloproliferative neoplasms; inflammatory signaling; targeted therapies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Acute myeloid leukemia is the most common type of leukemia in adults and is caused by the acquisition of somatic mutations in hematopoietic stem and progenitor cells mediating their transformation to malignant cells that dominate the bone marrow. Despite the extensive investigation of the molecular biology of AML and the introduction of numerous novel agents and combinational approaches for the treatment of this disease, the outcomes of AML patients and particularly older individuals and those with antecedent myeloid neoplasms remain poor overall. A deeper and better understanding of the molecular pathways mediating the growth and resistance of AML blasts is required to introduce new therapies especially for resistant and relapsed forms of AML. This can be achieved by collaborative approaches in AML research and better comprehension of the resistant patterns to the current therapeutic approaches.

This Special Issue discusses the recent discoveries related to the biology of AML, the current therapeutic landscape and possible mechanisms of resistance to the current treatments. This covers studies at the basic and translational level but also clinical studies with an emphasis on studies focusing on the characteristics of relapsed and treatment-resistant AMLs.

Dr. Theodoros Karantanos
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 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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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 myeloid leukemia
  • molecular biology
  • treatment landscape
  • resistance mechanisms

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Published Papers (5 papers)

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Research

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14 pages, 825 KiB  
Article
Salvage Therapy with Second-Generation Inhibitors for FLT3 Mutated Acute Myeloid Leukemia: A Real-World Study by the CETLAM and PETHEMA Groups
by Susana Vives, David Quintela, Mireia Morgades, Isabel Cano-Ferri, Alfons Serrano, Evelyn Acuña-Cruz, Marta Cervera, Marina Díaz-Beyá, Belén Vidriales, José Ángel Raposo-Puglia, Montserrat Arnan, Ana Garrido, Amaia Balerdi, Ana Isabel Cabello, Pilar Herrera-Puente, Josefina Serrano, Rosa Coll, Mar Tormo, Javier López-Marín, Sara García-Ávila, María Soledad Casado, Irene Padilla, Gabriela Rodríguez-Macías, María Calbacho, Ana Puchol, Agustín Hernández, Melissa Torres, Lissette Costilla, Maria Mercedes Colorado, David Martínez-Cuadrón, Jordi Esteve and Pau Montesinosadd Show full author list remove Hide full author list
Cancers 2024, 16(23), 4028; https://doi.org/10.3390/cancers16234028 - 30 Nov 2024
Viewed by 1357
Abstract
Background/Objectives: Patients with relapsed/refractory (R/R) AML with FLT3 mutation (FLT3mut) have a dismal prognosis. FLT3mut offers a target for therapy in these patients. Gilteritinib (gilter) and quizartinib (quizar) have demonstrated efficacy as single agents in two phase 3 clinical [...] Read more.
Background/Objectives: Patients with relapsed/refractory (R/R) AML with FLT3 mutation (FLT3mut) have a dismal prognosis. FLT3mut offers a target for therapy in these patients. Gilteritinib (gilter) and quizartinib (quizar) have demonstrated efficacy as single agents in two phase 3 clinical trials. Methods: We retrospectively analyzed the characteristics, treatments, and outcomes of 50 patients with R/R FLT3mut AML who received gilter or quizar as monotherapy in 27 Spanish centers before their commercial availability. Forty-four patients were treated with gilter and six with quizar. Results: The median age was 62.5 years, and 52% were women. Most patients presented with FLT3-ITD mutations (80%); 46% had refractory disease and 54% had relapsed disease at treatment initiation. First-line treatment was chemotherapy in 80% of patients, with 40% of these also receiving midostaurin. Twenty-five patients (50%) had previously received FLT3 inhibitor, and twenty-eight (56%) had received more than one line treatment before starting gilter/quizar. The rates of complete remission (CR), CR without hematological recovery (CRi), and partial remission were 22%, 18%, and 16%, respectively. The median overall survival (OS) and disease-free survival were 4.74 months and 2.99 months, respectively. We observed a significant improvement in OS in patients who had received only one prior line of therapy compared to those who had received two or more therapies (10.77 months vs. 4.24 months, p = 0.016). Multivariate analysis identified failure to achieve CR/CRi, receiving more than one prior line of therapy, age, and white blood cells count as independent prognostic factors for OS. The most common toxicities were febrile neutropenia, liver function abnormalities, and QT interval prolongation. Conclusions: Gilter/quizar monotherapy are effective and tolerable options for patients with R/R FLT3mut AML in a real-world setting. Response and toxicity rates are similar to those reported in the phase 3 trials, despite the more heterogeneous nature of the study population. Full article
(This article belongs to the Special Issue Acute Myeloid Leukemia in Adults)
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12 pages, 843 KiB  
Article
Patients with TP53-Mutated Acute Myeloid Leukemia Receiving Intensive Induction Therapy Have Superior Outcomes Due to a Higher Rate of Salvage Therapy: A Single Institution, Retrospective Study
by Nuttavut Sumransub, Gabriel K. Steinwand, Keith Cordner, Yoonkyu Lee, Qing Cao, Jeremy Allred, Veronika Bachanova, Mark Juckett, Craig Eckfeldt, Joseph E. Maakaron, Sean I. Tracy, Vidhyalakshmi Ramesh, Andrew C. Nelson, Sophia Yohe and Zohar Sachs
Cancers 2024, 16(16), 2784; https://doi.org/10.3390/cancers16162784 - 7 Aug 2024
Viewed by 1746
Abstract
Background: TP53 mutations (TP53m) define the most treatment-refractory acute myeloid leukemia (AML) subtype. Optimal treatment approaches have not been established in this setting. We reviewed our institutional experience to identify therapy sequencing, treatment response, and survival patterns in these patients. Methods: [...] Read more.
Background: TP53 mutations (TP53m) define the most treatment-refractory acute myeloid leukemia (AML) subtype. Optimal treatment approaches have not been established in this setting. We reviewed our institutional experience to identify therapy sequencing, treatment response, and survival patterns in these patients. Methods: This study was a single-center, retrospective cohort analysis. Results: Our cohort includes 86 TP53m and 337 TP53 wild-type (TP53wt) adult AML patients. TP53m AML patients presented with lower bone marrow and peripheral blasts; none presented with hyperleukocytosis. Patients who received intensive treatment up front demonstrated superior overall survival (OS) over those receiving first-line non-intensive therapy (2-year OS 22% versus 7%; p = 0.02). However, the complete remission (CR) rates among the first-line intensive and non-intensive therapy groups were comparable (21.9% and 29.4%, respectively, p = 0.49). The improved OS is therefore attributed to superior cumulative CR in the intensive group. First-line intensively treated patients were more likely to receive and respond to salvage, leading to a cumulative CR rate of 65.7% (versus 29.4%, p = 0.003). Achieving CR at any point is strongly associated with superior survival outcomes with 2-year OS of 31% versus 0% for those not achieving CR ever (p < 0.01). Conclusions: We find that TP53m AML rarely presents with oncological emergencies, suggesting that clinical trial enrollment is feasible in this group. Additionally, in our cohort, intensive induction therapies lead to superior survival outcomes attributed to successful salvage therapy. These data suggest that strategic therapy sequencing and salvage therapy may be important in optimizing outcomes for TP53m AML patients. Full article
(This article belongs to the Special Issue Acute Myeloid Leukemia in Adults)
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Review

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24 pages, 1770 KiB  
Review
Unraveling Venetoclax Resistance: Navigating the Future of HMA/Venetoclax-Refractory AML in the Molecular Era
by Theodora Chatzilygeroudi, Theodoros Karantanos and Vasiliki Pappa
Cancers 2025, 17(9), 1586; https://doi.org/10.3390/cancers17091586 - 7 May 2025
Viewed by 145
Abstract
Acute myeloid leukemia (AML) has traditionally been linked to a poor prognosis, particularly in older patients who are ineligible for intensive chemotherapy. The advent of Venetoclax, a powerful oral BH3 mimetic targeting anti-apoptotic protein BCL2, has significantly advanced AML treatment. Its combination with [...] Read more.
Acute myeloid leukemia (AML) has traditionally been linked to a poor prognosis, particularly in older patients who are ineligible for intensive chemotherapy. The advent of Venetoclax, a powerful oral BH3 mimetic targeting anti-apoptotic protein BCL2, has significantly advanced AML treatment. Its combination with the hypomethylating agent azacitidine (AZA/VEN) has become a standard treatment for this group of AML patients, demonstrating a 65% overall response rate and a median overall survival of 14.7 months, compared to 22% and 8 months with azacitidine monotherapy, respectively. However, resistance and relapses remain common, representing a significant clinical challenge. Recent studies have identified molecular alterations, such as mutations in FLT3-ITD, NRAS/KRAS, TP53, and BAX, as major drivers of resistance. Additionally, other factors, including metabolic changes, anti-apoptotic protein expression, and monocytic or erythroid/megakaryocytic differentiation status, contribute to treatment failure. Clinical trials are exploring strategies to overcome venetoclax resistance, including doublet or triplet therapies targeting IDH and FLT3 mutations; novel epigenetic approaches; menin, XPO1, and MDM2 inhibitors; along with immunotherapies like monoclonal antibodies and antibody–drug conjugates. A deeper understanding of the molecular mechanisms of resistance through single-cell analysis will be crucial for developing future therapeutic strategies. Full article
(This article belongs to the Special Issue Acute Myeloid Leukemia in Adults)
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19 pages, 1349 KiB  
Review
Inflammation and Related Signaling Pathways in Acute Myeloid Leukemia
by Nour Sabiha Naji, Mrudula Sathish and Theodoros Karantanos
Cancers 2024, 16(23), 3974; https://doi.org/10.3390/cancers16233974 - 27 Nov 2024
Cited by 4 | Viewed by 2756
Abstract
Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, and inflammatory signaling is involved in its pathogenesis. Cytokines exert a robust effect on the progression of AML and affect survival outcomes. The dysregulation in the cytokine network may foster a pro-tumorigenic microenvironment, increasing [...] Read more.
Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, and inflammatory signaling is involved in its pathogenesis. Cytokines exert a robust effect on the progression of AML and affect survival outcomes. The dysregulation in the cytokine network may foster a pro-tumorigenic microenvironment, increasing leukemic cell proliferation, decreasing survival and driving drug resistance. The dominance of pro-inflammatory mediators such as IL-11β, TNF-α and IL-6 over anti-inflammatory mediators such as TGF-β and IL-10 has been implicated in tumor progression. Additionally, inflammatory cytokines have favored certain populations of hematopoietic stem and progenitor cells with mutated clonal hematopoiesis genes. This article summarizes current knowledge about inflammatory cytokines and signaling pathways in AML, their modes of action and the implications for immune tolerance and clonal hematopoiesis, with the aim of finding potential therapeutic interventions to improve clinical outcomes in AML patients. Full article
(This article belongs to the Special Issue Acute Myeloid Leukemia in Adults)
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22 pages, 350 KiB  
Review
An Overview of Myeloid Blast-Phase Chronic Myeloid Leukemia
by Gulsum E. Pamuk and Lori A. Ehrlich
Cancers 2024, 16(21), 3615; https://doi.org/10.3390/cancers16213615 - 26 Oct 2024
Cited by 1 | Viewed by 2534
Abstract
Myeloid blast-phase chronic myeloid leukemia (MBP-CML) is a rare disease with a dismal prognosis. It is twice as common as lymphoid blast-phase CML, and its prognosis is poorer. Despite the success with tyrosine kinase inhibitors in the treatment of chronic-phase CML, the same [...] Read more.
Myeloid blast-phase chronic myeloid leukemia (MBP-CML) is a rare disease with a dismal prognosis. It is twice as common as lymphoid blast-phase CML, and its prognosis is poorer. Despite the success with tyrosine kinase inhibitors in the treatment of chronic-phase CML, the same does not hold true for MBP-CML. In addition to the Philadelphia chromosome, other chromosomal and molecular changes characterize rapid progression. Although some progress in elucidating the biology of MBP-CML has been made, there is need to discover more in order to develop more satisfactory treatment options. Currently, most common treatment options include tyrosine kinase inhibitors (TKIs) as monotherapy or in combination with acute myeloid leukemia-based intensive chemotherapy regimens. Some patients may develop resistance to TKIs via BCR-ABL1-dependent or BCR-ABL1-independent mechanisms. In this paper, we provide an overview of the biology of MBP-CML, the current treatment approaches, and mechanisms of resistance to TKIs. In order to improve treatment responses in these patients, more emphasis should be placed on understanding the biology of myeloid blastic transformation in CML and mechanisms of resistance to TKIs. Although patient numbers are small, randomized clinical trials should be considered. Full article
(This article belongs to the Special Issue Acute Myeloid Leukemia in Adults)
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