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Acute myeloid leukemia (AML) is a clonal disorder of myeloid lineage precursors. Identification of cytogenetic aberrations is essential for classification and risk stratification of AML, with many demonstrating unique associations with various clinicopathologic features. One such abnormality is MYC amplification, a rare occurrence identified in less than 1% of AML patients. MYC is most commonly amplified in the form of double minutes, but may also occur via ring and marker chromosomes or homogeneously staining regions. Amplification of MYC often involves various chromosomal aberrations, including trisomies 4 and 6 and aneusomy of the sex chromosomes. In many cases, the presence of MYC amplicons is also associated with other negative prognostic factors, including complex karyotype and advanced age. Although MYC has been extensively investigated as a therapeutic target in various cancers, there are few studies examining the clinical significance of MYC amplification in AML. In this review, we explore recurrent cytogenetic abnormalities and demographic characteristics associated with amplification of MYC in patients with AML and discuss their diagnostic and therapeutic implications.
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Discov Oncol
August 2025
Department of Internal Medicine, School of Medicine, Cancer Prevention Research Center, Seyyed Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
All forms of leukemia, including AML, ALL, CML, and CLL, are estimated to make up 2.5% of new cancer diagnoses and 3.1% of all cancer fatalities worldwide.
View Article and Find Full Text PDFJ Med Chem
August 2025
Janssen Research & Development, Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Myeloid Cell Leukemia 1, or MCL-1, is an anti-apoptotic protein belonging to the BCL-2 family of proteins, which regulate the mitochondrial pathway of cellular apoptosis via binding of pro- and anti-apoptotic family members. Genetic amplification and overexpression of MCL-1 is one mechanism cancer cells utilize to avoid death and thus MCL-1 has emerged as an attractive target for cancer treatment. Herein, we describe our strategy and medicinal chemistry efforts to identify best-in-class MCL-1 inhibitors with high cytotoxic potency and improved biorelevant solubility while aiming to maximize therapeutic index versus on-target toxicity via IV dosing.
View Article and Find Full Text PDFJ Clin Invest
August 2025
Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, United States of America.
Mutations that initiate AML can cause clonal expansion without transformation ("clonal hematopoiesis"). Cooperating mutations, usually in signaling genes, are needed to cause overt disease, but these may require a specific "fitness state" to be tolerated. Here, we show that nearly all AMLs arising in a mouse model expressing two common AML initiating mutations (Dnmt3aR878H and Npm1cA) acquire a single copy amplification of chromosome 7, followed by activating mutations in signaling genes.
View Article and Find Full Text PDFBr J Haematol
August 2025
Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Tumour protein p53 (TP53) mutations occur frequently in myelodysplastic syndromes (MDS) and are associated with a high risk of treatment failure and adverse outcomes. In this study, we analysed 1219 patients with MDS, focusing on the clinical and molecular characteristics of those with TP53 mutations and investigating factors contributing to worse survival and disease progression. One hundred and fifteen (9.
View Article and Find Full Text PDFCancers (Basel)
July 2025
Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy.
Immune checkpoints such as PD-1/PD-L1, CTLA-4, LAG-3, TIM-3, and TIGIT play critical roles in regulating anti-tumor immunity and are exploited by hematological malignancies to evade immune surveillance. While classic Hodgkin lymphoma (HL) demonstrates notable responsiveness to immune checkpoint inhibitors (ICIs), which is attributed to genetic alterations like chromosome 9p24.1 amplification, the responsiveness of non-Hodgkin lymphoma (NHL), acute myeloid leukemia (AML), and multiple myeloma (MM) remain inconsistent and generally modest.
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