Background: Chronic myeloid leukemia (CML) is a clonal malignant myeloproliferative disorder characterized by the expansion of hematopoietic cells carrying the Philadelphia chromosome (t 9.22). Our main objective was to assess the efficacy of imatinib in CML patients, measured by their survival.
Methods: Over a six-year period (June 2003 through May 2009), 25 patients were seen regularly for CML at the Lomé Campus teaching hospital. Patients received imatinib after diagnosis and underwent regular laboratory monitoring (quantification of BCR-ABL ratio by RT-PCR). Patients' survival and treatment response were evaluated.
Results: Patients' mean age at diagnosis was 40 years (range: 9 to 72 years). Men predominated (17 compared with 7 women). Splenomegaly was found in 80% of cases. The mean leukocyte level was 188.71 g/L (24.4-350). Six patients (24%) had thrombocytosis with a mean platelet count of 491.15 g/L (108-2000). Six patients (24%) died after developing accelerated-phase CML or blast crisis. Estimated overall survival of patients at 6 years was 60%. Molecular biology monitoring detected a secondary G250E mutation with resistance to imatinib in one patient. Standard hematological side effects led to reduction in imatinib doses. The principal nonhematological side effects were weight gain and transient digestible disorders.
Conclusions: At six years after diagnosis, imatinib was effective in treating patients with CML, even in sub-Saharan Africa. Mutation-induced resistance required regular molecular biological monitoring to determine the need to switch to later-generation tyrosine kinase inhibitors.
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http://dx.doi.org/10.1684/mst.2012.0083 | DOI Listing |
Acta Neurol Belg
January 2025
Departamento de Radiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brasil.
Adv Protein Chem Struct Biol
January 2025
Laboratory of Integrative Genomics, Department of Integrative Biology, School of BioSciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India. Electronic address:
The prognosis for mixed-lineage leukemia (MLL), particularly in young children, remains a significant health concern due to the limited therapeutic options available. MLL refers to KMT2A chromosomal translocations that produce MLL fusion proteins. The protein menin, which is essential for the malignant potential of these MLL fusion proteins, offers novel targets for acute leukemia treatment.
View Article and Find Full Text PDFCell Genom
January 2025
Early Cancer Institute, University of Cambridge, Cambridge, UK. Electronic address:
The representation of driver mutations in preleukemic hematopoietic stem cells (pHSCs) provides a window into the somatic evolution that precedes acute myeloid leukemia (AML). Here, we isolate pHSCs from the bone marrow of 16 patients diagnosed with AML and perform single-cell DNA sequencing on thousands of cells to reconstruct phylogenetic trees of the major driver clones in each patient. We develop a computational framework that can infer levels of positive selection operating during preleukemic evolution from the statistical properties of these phylogenetic trees.
View Article and Find Full Text PDFBlood
January 2025
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States.
Stemness-associated cell states are linked to chemotherapy resistance in AML. We uncovered a direct mechanistic link between expression of the stem cell transcription factor GATA2 and drug resistance. The GATA-binding protein 2 (GATA2) plays a central role in blood stem cell generation and maintenance.
View Article and Find Full Text PDFLangmuir
January 2025
Zhejiang Cancer Hospital, The Key Laboratory of Zhejiang Province for Nucleic Acids, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
Surface antigen-directed immunotherapy is a curative treatment modality for acute myeloid leukemia (AML) that is characterized by the abundance and stability expression of surface antigens. However, current surface antigen-directed immunotherapies have shown poor outcomes and undesirable mortality rates in treating AML patients, primarily due to acquired resistance that arises from using single-target therapies to address the heterogeneous expression of surface antigens. Hence, in order to improve the efficacy of antigen-specific therapies for treating AML, we designed a bispecific aptamer-drug conjugate.
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