Chronic Myeloid Leukemia

In addition, we assessed the effect of gene polymorphisms on the course of the disease, and rapid disease progression was found to be correlated with the presence of these polymorphisms. These findings could help determine the risk of developing MPNs and patient prognosis.

The most used agents include hydroxyurea, interferon, hypomethylating agents, and JAK inhibitors, although none of them are disease-modifying. Allogeneic hematopoietic stem cell transplant remains the only potentially curative approach and should be considered in all eligible patients. Actionable mutations (CSF3R, NRAS/KRAS, and KIT) have also been identified, supporting the development of new agents targeting the involved pathways.

The rare genetic co-occurrence of t(15;17)/PML::RARA and t(9;22)/BCR::ABL1 translocations may be identified in a single patient with acute promyelocytic leukaemia (APL).Successful induction using all-trans retinoic acid (ATRA) together with imatinib achieved effective control of both leukemic clones.The patient demonstrated rapid haematologic remission and favourable clinical recovery, suggesting a positive outcome with this therapeutic approach.

Since then, four other tyrosine kinase inhibitors (TKIs), dasatinib, nilotinib, bosutinib and most recently asciminib, have garnered approval for frontline management of CML-CP. With limited prospective comparisons between the 2G-TKIs and similar survival outcomes with imatinib compared to 2G-TKIs, the selection of a TKI for patients with newly diagnosed CML-CP must be individualized to the needs of that specific patient. Important factors to consider when choosing a drug include patient related factors (age, comorbidities, lifestyle considerations, quality of life, patient preferences, shared-decision making and whether treatment free remission [TFR] is a goal), disease related factors (risk stratification, transcript type, presence of high risk gene mutations such as ASXL1) and drug related factors (major molecular response rates with each TKI, adverse events, rates of treatment discontinuation and TFR rates).

The visual and texture features of the Siamese architecture help in the capture of molecular similarities based on electrostatic and non-covalent interaction profiles. Therefore, the developed protocol offers a suitable approach in computational drug discovery, being a promising framework for virtual screening, drug repositioning, and the identification of novel therapeutic candidates.

Modulating the miR-122-5p/CDC25A axis may provide potential molecular targets for inhibiting CML progression through regulation of cell cycle pathways. Findings are exploratory and based on bioinformatics with limited in vitro expression confirmation; functional studies are required to establish causality.

One of the mutations that is still an on-going challenge in clinical and scientific field is the T315I mutation, since it gives patients a poor prognosis attributable to acquired resistance to therapy. In the following narrative review, we will discuss the current knowledge on the T315I mutation, explore the most suitable treatment options, examine the role of third-generation tyrosine kinase inhibitors, and outline potential future therapeutic strategies.

Pin1 may convert the mature form BCR::ABL1 to an immature form for Bag1 recognition leading to CHIP-mediated ubiquitination and degradation. These findings may lead to provide a molecular basis for the development of new Pin1 related therapeutic strategies against TKI resistance.

However, the toxicity and resistance associated with the use of imatinib, a first-generation Bcr-Abl inhibitor, in cases where the T315I mutation exists, necessitates the need for new tyrosine kinase inhibitors...However, investigating different combined scaffolds enhances the chance of successfully developing novel drug candidates. Overall, the information provided in this review can be beneficial to researchers with an interest in chronic myeloid leukemia and tyrosine kinase inhibitors.

P=N/A, N=5000, Recruiting, University of Alabama at Birmingham | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2026 --> Dec 2027