N6-methyladenosine (m6A) RNA modification in chronic myeloid leukemia: unveiling a novel therapeutic target.

N6-methyladenosine (m6A), the most prevalent internal mRNA modification, plays a critical role in physiological processes by regulating gene expression through modulation of mRNA metabolism at multiple stages. In recent years, m6A has garnered significant attention for a deeper understanding of the initiation, progression, and drug resistance of various cancers, including hematological malignancies. Dysregulation of m6A has been implicated in both cancer promotion and suppression. m6A methylation is a complex regulatory process involving methyltransferases (writers), demethylases (erasers), and proteins that recognize specific m6A modifications (readers). This intricate interplay presents challenges for precisely modulating m6A levels, either globally or at specific sites. This review specifically focuses on the role of m6A in chronic myeloid leukemia (CML), a blood cancer characterized by the BCR-ABL1 fusion. We emphasize its impact on leukemia cell survival and drug resistance mechanisms. Notably, inhibitors targeting m6A regulators show promise in preclinical models, suggesting a potential therapeutic avenue for CML. Integrating our understanding of m6A biology with current treatment strategies may lead to more effective therapies, especially for patients with advanced-stage or resistant CML.

Multiple Roles of m6A RNA Modification in Translational Regulation in Cancer.

Despite its discovery in the early 1970s, m6A modification within mRNA molecules has only powerfully entered the oncology field in recent years. This chemical modification can control all aspects of the maturation of mRNAs, both in the nucleus and in the cytoplasm. Thus, the alteration in expression levels of writers, erasers, and readers may significantly contribute to the alteration of gene expression observed in cancer. In particular, the activation of oncogenic pathways can lead to an alteration of the global rate of mRNA translation or the selective translation of specific mRNAs. In both cases, m6A can play an important role. In this review, we highlight the role of m6A in the regulation of translation by focusing on regulatory mechanisms and cancer-related functions of this novel but still controversial field.

[Diagnostic accuracy of an automatic blood pressure device for ankle brachial index determination in ischemic stroke patients]. / Precisión diagnóstica de un dispositivo automático en la determinación del índice tobillo-brazo en pacientes con ictus isquémico.

INTRODUCTION: Ankle brachial index (ABI) is not widespread in clinical practice because the need for specific equipment and training. Doing it without these requirements, quicker and with a cheaper method would facilitate their routine use. AIMS: To evaluate sensitivity and specificity of an automatic blood pressure device detecting ABI < 0.90, when technique is performed by nurses. To evaluate agreement between two techniques for the ABI determination. PATIENTS AND METHODS. Diagnostic accuracy study in 30 ischemic stroke patients. For each patient, three measurements were performed with the automatic device, and one with the reference method. RESULTS: The automatic blood pressure device performance detecting ABI < 0.90 was acceptable for each of the three measurements (sensitivity: 78%, 87% and 100%; specificity: 95%, 100% and 100%; positive predictive value: 87%, 100% and 100%; negative predictive value: 91%, 96% y 100%; accuracy: 90%, 97% y 100%). The intraclass correlation coefficients for intra-observer, inter-observer and inter-method variability showed acceptable levels, with results of 0.64, 0.83 and 0.75, respectively. In the Bland Altman test only inter-method comparison had less than 5% of its values out of range. CONCLUSIONS: Sensitivity and specificity of an automatic blood pressure device detecting ABI < 0.90 shows acceptable levels when technique is performed by nurses. This suggests its potential as screening tool in transient ischemic attack/ischemic stroke patients.