Agnieszka Wierzbowska

Background: Secondary acute promyelocytic leukemia (sAPL) is a very rare subtype of acute myeloid leukemia that develops following exposure to chemotherapy, radiotherapy, or immunosuppressive agents. The treatment results and survival outcomes of sAPL patients are still not precisely defined. Methods: A search of the Polish Adult Leukemia Group (PALG) database identified 29 cases of sAPL (median age 57 years; 62.1% female) among 437 APL patients (6.7%) diagnosed between 2006 and 2024. Each sAPL case was matched to a de novo APL patient by sex, age, year of diagnosis, and treatment protocol (LPA (Leucemia Promielocítica Aguda) 2005, LPA 2012, or LPA 2017). Results: All sAPL cases occurred following chemo- and/or radiotherapy, most commonly for breast cancer. The sAPL cases demonstrated higher CD15 expression than the de novo APL cases (median 27.6% vs. 7%, p = 0.04). The two groups exhibited comparable complete remission rates (82.8% sAPL vs. 75.9% de novo; p = 0.75) and early mortality rates (17.2% vs. 20.7%, p = 1.0). However, relapse-free survival was significantly shorter in sAPL (median 94.7 months vs. not reached; HR 7.23, 95% CI 1.63–32.02, p = 0.030), whereas overall survival did not differ significantly between groups. Multivariate analysis identified Eastern Cooperative Oncology Group performance status ≥3 and CD15 expression > 20% as independent predictors of inferior survival. Conclusions: These findings suggest that sAPL shares many clinical features with de novo APL but carries a higher risk of relapse, highlighting the need for further prospective studies and the potential implementation of tailored therapeutic strategies.

Chimeric antigen receptor (CAR) T-cell therapy represents a major advance in modern immunotherapy. This narrative review summarizes evidence from the past five years, including case reports, case series, and clinical trials, on its application beyond hematologic malignancies, focusing on autoimmune diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), as well as solid tumors including melanoma and primary cutaneous lymphomas. CD19-directed CAR T-cells have demonstrated clinical benefits in SLE and SSc, with sustained immune reset, reduced autoreactive antibody levels, and clinical improvement. In melanoma, CAR T-cells targeting GD2, cMET, and CD20 have shown in vivo expansion and tumor infiltration; however, clinical efficacy remains limited, with transient stabilization or disease progression in most patients. In primary cutaneous lymphomas, early-phase studies with anti-CD70 and anti-CCR4.30 CAR T-cells indicate partial tumor regression and disease stabilization, often requiring additional therapy. Key challenges include limited durability of immune reset due to persistent plasma cells in autoimmune disorders, tumor heterogeneity, antigen loss or overlap, infiltration barriers, resistance mechanisms, and T-cell depletion in solid tumors, collectively reducing response durability and safety. The main toxicities include grade 1–2 cytokine release syndrome and rare hematologic complications, while immune effector cell-associated neurotoxicity syndrome is uncommon. Clinical translation remains limited and requires larger studies to improve efficacy and define safety profiles.

Chimeric antigen receptor (CAR) T cell therapy represents one of the greatest breakthroughs in modern immunotherapies. To date, it has been approved by the Food and Drug Administration (FDA) for the treatment of several hematological malignancies, including different subtypes of leukemia, lymphoma, and multiple myeloma. However, recent reports suggest that CAR T therapy may also be effective in the treatment of severe systemic autoimmune diseases, such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Case reports and small case series have demonstrated the efficacy of anti-CD19 CAR T cell therapy while maintaining a favorable safety profile. The most frequently reported adverse events include grade 1 or 2 cytokine release syndrome (CRS), hypogammaglobulinemia, and mild infectious complications. Moreover, CAR T therapy may also have potential in the treatment of advanced metastatic solid tumors, including melanoma. Early clinical studies have demonstrated the feasibility and safety of CAR T cell therapy in metastatic melanoma; however, several challenges remain. These include limited tumor trafficking and infiltration of CAR T cells, due to the presence of an immunosuppressive tumor microenvironment. Additionally, following the remarkable success of CAR T therapy in lymphomas, this approach may also be applied to the treatment of cutaneous lymphomas, including cutaneous T-cell and B-cell lymphomas. Key challenges include tumor heterogeneity, optimal target antigen selection, fratricidal activity of CAR T cells, and potential contamination of the CAR T product with lymphoma cells.

Measurable residual disease (MRD) monitoring has become a critical component in the management of acute myeloid leukemia (AML), to inform prognosis, guide therapy, and serve as a key end point in clinical trials. The 2025 update of the MRD guideline provides a comprehensive and refined framework for MRD assessment, aligned with the European LeukemiaNet (ELN) 2022 genetic risk classification. Developed by members of the ELN AML MRD Working Party, the guidelines incorporate expert consensus determined through a 2-stage Delphi round. They address the clinical implementation of MRD methodologies, technical considerations, integration into clinical trials, and future directions. Importantly, MRD recommendations are tailored to individual prognostic and genetic subgroups. A new qualitative MRD response category, designated as optimal, warning, or high risk of treatment failure, has been introduced to facilitate contextual interpretation of the MRD burden and its clinical relevance. Notably, ultrahigh-sensitivity next-generation sequencing–based MRD assessment is now recommended for FLT3 internal tandem duplication–mutated AML after intensive chemotherapy and before allogeneic hematopoietic cell transplantation. A total of 56 recommendations were formulated, with 53 achieving a high level of consensus (≥90%). These updated guidelines represent a major step forward toward harmonizing MRD assessments in AML and enhancing its clinical utility across diverse treatment settings.

Fitness assessment in patients with acute myeloid leukemia (AML) is critical to deliver the right therapy to the right patient. Although several scoring systems are available to aid in determining fitness, the absence of validation studies has resulted in the lack of universally accepted assessment procedures. This limitation, combined with the increasing availability of novel agents expanding the spectrum of less-intensive options, has introduced additional complexity to the fitness assessment process. In this evolving context, fitness should reflect eligibility for a specific treatment among the several available, rather than a generic binary classification of eligibility for intensive chemotherapy. Moreover, the growing emphasis on patient-centered care, further highlights the importance of integrating quality of life, patient preferences, patient self-reported physical and social functioning status, social support, and early integration of palliative care into the assessment framework. A modern interpretation of fitness assessment should incorporate a comprehensive evaluation that extends beyond traditional clinical and biological disease characteristics. Thus, fitness assessment in patients with AML represents only 1 piece of a larger puzzle, encompassing the patient’s overall capacity to sustain and benefit from a specific therapeutic program.

MicroRNA (miRNA), a significant class of regulatory non-coding RNA (ncRNA), can regulate the expression of numerous protein-coding messenger RNAs (mRNAs). miRNA plays an important part in shaping the human transcriptome. So far, in the human genome, about 2500 miRNAs have been found. Acute myeloid leukemia (AML) belongs to a malignant clonal disorder of hematopoietic stem cells and is characterized by the uncontrolled clonal proliferation of abnormal progenitor cells in the bone marrow and blood. For the past several years, significant scientific attention has been attracted to the role of miRNAs in AML, since alterations in the expression levels of miRNAs may contribute to AML development. This review describes the main functions of non-coding RNA classes and presents miRNA biogenesis. This study aims to review recent reports about altered microRNA expression and their influence on AML cell survival, cell cycle, and apoptotic potential. Additionally, it summarizes the correlations between miRNAs and their target mRNAs in AML and outlines the role of particular miRNAs in AML subtypes according to ELN recommendations.

Acute myeloid leukemia (AML) corresponds to a heterogeneous group of clonal hematopoietic diseases, which are characterized by uncontrolled proliferation of malignant transformed myeloid precursors and their inability to differentiate into mature blood cells. The prognosis of AML depends on many variables, including the genetic features of the disease. Treatment outcomes, despite the introduction of new targeted therapies, are still unsatisfactory. Recently, there have been an increasing number of reports on enzymatic proteins of the sirtuin family and their potential importance in cancer in general. Sirtuins are a group of 7 (SIRT1-7) NAD+-dependent histone deacetylases with pleiotropic effects on metabolism, aging processes, and cell survival. They are not only responsible for post-translational modification of histones but also play various biochemical functions and interact with other proteins regulating cell survival, such as p53. Thus, their role in key mechanisms of tumorigenesis makes them a worthwhile topic in AML. Different sirtuins have been shown to act oppositely depending on the biological context, the mechanism of which requires further exploration. This review provides a comprehensive description of the significance and role of sirtuins in AML in light of the current state of knowledge. It focuses in particular on molecular mechanisms regulated by sirtuins and signaling pathways involved in leukemogenesis, as well as clinical aspects and potential therapeutic targets in AML.

Acute myeloid leukemia (AML) corresponds to a heterogeneous group of clonal hematopoietic diseases, which are characterized by uncontrolled proliferation of malignant transformed myeloid precursors and their inability to differentiate into mature blood cells. The prognosis of AML depends on many variables, including the genetic features of the disease. Treatment outcomes, despite the introduction of new targeted therapies, are still unsatisfactory. Recently, there have been an increasing number of reports on enzymatic proteins of the sirtuin family and their potential importance in cancer in general. Sirtuins are a group of 7 (SIRT1-7) NAD+-dependent histone deacetylases with pleiotropic effects on metabolism, aging processes, and cell survival. They are not only responsible for post-translational modification of histones but also play various biochemical functions and interact with other proteins regulating cell survival, such as p53. Thus, their role in key mechanisms of tumorigenesis makes them a worthwhile topic in AML. Different sirtuins have been shown to act oppositely depending on the biological context, the mechanism of which requires further exploration. This review provides a comprehensive description of the significance and role of sirtuins in AML in the light of the current state of knowledge. It focuses in particular on molecular mechanisms regulated by sirtuins and signaling pathways involved in leukemogenesis, as well as clinical aspects and potential therapeutic targets in AML.

The European LeukemiaNet (ELN) genetic risk classifications were developed based on data from younger adults receiving intensive chemotherapy. Emerging analyses from patients receiving less-intensive therapies prompted a proposal for an ELN genetic risk classification specifically for this patient population.