A 51-year-old man with chronic myeloid leukemia (CML) was treated with imatinib (IM). After 24 months of treatment, he achieved a complete molecular response (CMR), which he sustained for 3 years. However, 4 months after discontinuing IM treatment, the CML relapsed. The patient was treated again with IM and achieved CMR. A combination of IM and interferon-α (IFNα) was administered for the following year, and then discontinued. The patient has since sustained CMR without therapy for 24 months, to date. This patient was found to have a BCL2L11 (BIM) deletion polymorphism. CML patients with a BIM deletion polymorphism show a low response to IM, and we infer that the BIM deletion polymorphism is a negative factor for discontinuation of IM. IFNα treatment is expected to prevent relapse during immunological surveillance. Therefore, the combination of IM and IFNα might be a feasible approach for CML patients who experience difficulty with IM discontinuation.
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http://dx.doi.org/10.11406/rinketsu.56.216 | DOI Listing |
Leukemia
October 2024
Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore, 169857, Singapore.
One sixth of human cancers harbor pathogenic germline variants, but few studies have established their functional contribution to cancer outcomes. Here, we developed a humanized mouse model harboring a common East Asian polymorphism, the BIM deletion polymorphism (BDP), which confers resistance to oncogenic kinase inhibitors through generation of non-apoptotic splice isoforms. However, despite its clear role in mediating bulk resistance in patients, the BDP's role in cancer stem and progenitor cells, which initiate disease and possess altered BCL-2 rheostats compared to differentiated tumor cells, remains unknown.
View Article and Find Full Text PDFJ Ethnopharmacol
January 2025
Innovation Center for Medical Basic Research of Autoimmune Diseases, China National Ministry of Education, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China. Electronic address:
Ethnopharmacological Relevance: Jieduquyuziyin prescription (JP) is an empirical prescription approved for application to treat systemic lupus erythematosus (SLE) in hospital within China. Despite the prominent treatment effect of JP clinically, further investigation is imperative to explore its underlying mechanisms.
Aim Of The Study: We aim to investigate the impact of JP on DN T cell apoptosis in the treatment of SLE and the specific regulation mechanisms.
Exp Eye Res
November 2024
McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Electronic address:
Apoptosis plays prominent roles during organ development, maturation and homeostasis. In the retina, Bcl-2 family members function through the intrinsic cell death pathway with vital roles during vascular development and hyperoxia-mediated vessel obliteration during oxygen induced ischemic retinopathy (OIR). Bim, a BH3 only protein Bcl-2 family member, binds and activates Bax and/or Bak to facilitate apoptosis.
View Article and Find Full Text PDFCell Death Dis
September 2024
Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Faculty of Medicine, Freiburg, Germany.
Myeloid cells are the first line of defence against pathogens. Mitochondrial apoptosis signalling is a crucial regulator of myeloid cell lifespan and modulates the function of myeloid cells. The anti-apoptotic protein BCL-2-family protein BCL2A1/A1/BFL-1 is strongly upregulated in inflammation in macrophages.
View Article and Find Full Text PDFJ Exp Med
October 2024
Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
The translocation t(14;18) activates BCL2 and is considered the initiating genetic lesion in most follicular lymphomas (FL). Surprisingly, FL patients fail to respond to the BCL2 inhibitor, Venetoclax. We show that mutations and deletions affecting the histone lysine methyltransferase SETD1B (KMT2G) occur in 7% of FLs and 16% of diffuse large B cell lymphomas (DLBCL).
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