Overcoming flumatinib resistance in chronic myeloid leukaemia: Insights into cellular mechanisms and ivermectin's therapeutic potential.

Chronic myeloid leukaemia (CML) is a haematological malignancy characterized by the constitutive tyrosine kinase activity of the BCR-ABL1 fusion protein. Flumatinib, a second-generation tyrosine kinase inhibitor, has exhibited superior clinical efficacy compared to its precursor, imatinib. However, with increased clinical use, resistance to flumatinib has emerged as a significant challenge.

SF-Transformer: A Mutual Information-Enhanced Transformer Model with Spot-Forward Parity for Forecasting Long-Term Chinese Stock Index Futures Prices.

The complexity in stock index futures markets, influenced by the intricate interplay of human behavior, is characterized as nonlinearity and dynamism, contributing to significant uncertainty in long-term price forecasting. While machine learning models have demonstrated their efficacy in stock price forecasting, they rely solely on historical price data, which, given the inherent volatility and dynamic nature of financial markets, are insufficient to address the complexity and uncertainty in long-term forecasting due to the limited connection between historical and forecasting prices. This paper introduces a pioneering approach that integrates financial theory with advanced deep learning methods to enhance predictive accuracy and risk management in China's stock index futures market.

Patient Versus Physician Perspective in the Management of Chronic Myeloid Leukemia During Treatment with Tyrosine Kinase Inhibitors.

Introduction: Chronic myeloid leukemia (CML) is a chronic disease with treatment-free remission (TFR) increasingly regarded as a feasible goal of treatment. However, various factors may influence adherence to international guidelines for CML management. This study aimed to compare the reporting of care between patients with CML and their treating doctors.

De-escalation or discontinuation of tyrosine kinase inhibitor in patients with chronic myeloid leukemia: A multicentral, open-label, prospective trial in China.

: Long-term treatment-free remission (TFR) represents a new goal for chronic myeloid leukemia (CML). Optimizing dose of tyrosine kinase inhibitors (TKIs) in the CML treatment maybe a new challenge to maintain effective and improving patients' quality of life. We hypothesized that administration of low-dose TKIs does not compromise major molecular response (MMR) in patients with CML who have a deep molecular response (DMR).

Multi-Scale Influencing Factors and Prediction Analysis: Dongxing Port-City Relationship.

This study calculates the dynamic concentration index, explores the evolution of the relationship between the Dongxing port and city, and predicts its future. The results indicate that the relationship between the port and city has three development stages, namely the low-level balanced development stage (2001−2008), the port development stage (2009−2014), and the urban development stage (2015−2019). Based on the country (China and Vietnam), province (Guangxi Zhuang Autonomous Region), district (Fangchenggang City), county (Dongxing City), and individual (resident) levels, a multi-scale index system of influencing factors was developed.

Integrative Genomic Analysis Reveals Cancer-Associated Gene Mutations in Chronic Myeloid Leukemia Patients with Resistance or Intolerance to Tyrosine Kinase Inhibitor.

Introduction: While the acquisition of mutations in the ABL1 kinase domain (KD) has been identified as a common mechanism behind tyrosine kinase inhibitor (TKI) resistance, recent genetic studies have revealed that patients with TKI resistance or intolerance frequently harbor one or more genetic alterations implicated in myeloid malignancies. This suggests that additional mutations other than ABL1 KD mutations might contribute to disease progression.

Methods: We performed targeted-capture sequencing of 127 known and putative cancer-related genes of 63 patients with CML using next-generation sequencing (NGS), including 42 patients with TKI resistance and 21 with TKI intolerance.

[Clinical characteristics of chronic myeloid leukemia with T315I mutation and the efficacy of ponatinib].

Objective: To analyze the clinical features of chronic myeloid leukemia (CML) with T315 I mutation (CML-T315I) and compare the effectiveness of different treatments.

Methods: We retrospectively analyzed the clinical data and outcomes of 19 patients with CML-T315I receiving different treatments. The T315 I mutations in these patients were detected by examination of BCR-ABL kinase domain (KD) mutation by RTQ-PCR and Sanger sequencing.

Inhibition of Siah2 Ubiquitin Ligase by Vitamin K3 Attenuates Chronic Myeloid Leukemia Chemo-Resistance in Hypoxic Microenvironment.

BACKGROUND A hypoxic microenvironment is associated with resistance to tyrosine kinase inhibitors (TKIs) and a poor prognosis in chronic myeloid leukemia (CML). The E3 ubiquitin ligase Siah2 plays a vital role in the regulation of hypoxia response, as well as in leukemogenesis. However, the role of Siah2 in CML resistance is unclear, and it is unknown whether vitaminK3 (a Siah2 inhibitor) can improve the chemo-sensitivity of CML cells in a hypoxic microenvironment.

[Establishing the Ion Torrent PGM Sequencing Methods for the Clinical Diagnosis of MPN Patients].

Objective: To investigate the feasibility and relibility of rapidly and accurately acquiring the informations of gene mutations in MPN patients by using self-designed custom MPN mutation-related multipe-PCR primer kit and next generation Ion Torrent PGM sequencing platform.

Methods: The bone marrow samples of 10 MPN patients with JAK2V617F and/or CALR, Ph confirmed by sanger sequencing method were collected and were re-detected by using next generation Ion Torrent PGM sequencing method, then the consistence of results of above-mentioned 2 kinds of detection methods was compared.

Results: In terms of JAK2V617F, MPL and CALR mutations, the results of Ion Torrent PGM sequencing were complete consistent with results of Sanger sequencing, except 52 bp deletion of CALR gene, which conld not be detected by next generation Ion Torrent PGM sequencing method in all bone marrow samples.

Therapeutic immune monitoring of CD4CD25 T cells in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors.

Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib, are effective forms of therapy for various types of solid cancers and Philadelphia chromosome-positive (Ph) chronic myeloid leukemia. A number of TKIs have been known to have strong effects on T cells, particularly cluster of differentiation (CD) 4CD25 T cells, also known as regulatory T cells (Tregs). There is currently a deficit in the available clinical data regarding this area of study.

Correlation between deletion of the CDKN2 gene and tyrosine kinase inhibitor resistance in adult Philadelphia chromosome-positive acute lymphoblastic leukemia.

Background: Frequency relapses are common in Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) following tyrosine kinase inhibitors (TKIs). CDKN2A/B is believed to contribute to this chemotherapy resistance.

Methods: To further investigate the association between CDKN2 status and TKI resistance, the prevalence of CDKN2 deletions and its correlation with a variety of clinical features was assessed in 135 Ph-positive ALL patients using interphase fluorescence in situ hybridization (I-FISH).

CDKN2 Gene Deletion as Poor Prognosis Predictor Involved in the Progression of Adult B-Lineage Acute Lymphoblastic Leukemia Patients.

Deletion of cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) is well known in many hematologic malignancies, but only few reports have investigated this deletion effect on clinical prognosis. This study performed analysis of the CDKN2 deletion in 215 adult B- lineage acute lymphoblastic leukemia (B-ALL) patients, and related cytogenetic prognostic factors (BCR/ABL; E2A/PBXl; TEL/AML1; Mixed Lineage Leukemia (MLL) rearrangement; MYC, Immunoglobulin heavy locus (IGH) translocation). The prevalence of CDKN2 deletions in all study populations was 28.

Prognostic Significance of Monosomal Karyotype in Adult Patients With Acute Myeloid Leukemia Treated With Risk-Adapted Protocols.

Background: The monosomal karyotype (MK) is a well-known adverse prognostic factor and has been found to be related to poor outcome in patients with acute myeloid leukemia (AML). However, the outcome in MK-positive AML patients undergoing different therapies has not been well investigated.

Patients And Methods: We retrospectively analyzed clinical and laboratory features in 225 MK-positive AML patients.