We recently showed that cellular origin impacts the aggressiveness and the phenotype of acute myeloid leukemia (AML). Direct induction of the MLL-AF9 fusion in various hematopoietic compartments using a doxycycline (DOX) regulated mouse model (iMLL-AF9) led to an invasive chemoresistant AML expressing several genes known to be involved in epithelial to mesenchymal transition (EMT) in solid cancers. Many of these genes play important roles in migration and invasion and are significantly associated with poor overall survival in AML patients.
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http://dx.doi.org/10.1080/23723556.2016.1241854 | DOI Listing |
Cancers (Basel)
January 2025
Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Falmer, Brighton BN1 9PX, UK.
Background/objectives: Acute myeloid leukemia (AML) is an aggressive neoplasm. Although most patients respond to induction therapy, they commonly relapse due to recurrent disease in the bone marrow microenvironment (BMME). So, the disruption of the BMME, releasing tumor cells into the peripheral circulation, has therapeutic potential.
View Article and Find Full Text PDFCancers (Basel)
December 2024
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Richter transformation (RT) is a rare albeit devastating complication of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). RT is defined as an aggressive lymphoma, typically diffuse large B-cell lymphoma, in the setting of CLL. A clonal relationship to the preceding CLL clone is detected in the majority of RT cases and confers more aggressive clinicopathologic kinetics, resistance to standard chemoimmunotherapy regimens, and inferior survival.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Acute myeloid leukemia (AML) is an aggressive malignancy that poses significant challenges due to high rates of relapse and resistance to treatment, particularly in older populations. While therapeutic advances have been made, survival outcomes remain suboptimal. The evolution of DNA and RNA sequencing technologies, including whole-genome sequencing (WGS), whole-exome sequencing (WES), and RNA sequencing (RNA-Seq), has significantly enhanced our understanding of AML at the molecular level.
View Article and Find Full Text PDFLangerhans cell histiocytosis (LCH), juvenile xanthogranuloma (JXG) family lesions, and Rosai-Dorfman-Destombes disease (RDD) are now classified by the World Health Organization (WHO) under the heading of histiocytic/dendritic cell neoplasms. Each disease may manifest as a focal lesion, as multiple lesions, or as a widespread aggressive systemic disease with visceral organ involvement. Erdheim-Chester disease (ECD) is a rare systemic disease process of adults with limited cases in children.
View Article and Find Full Text PDFNat Struct Mol Biol
January 2025
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA.
The epigenetic cofactor ENL (eleven-nineteen-leukemia) and the acetyltransferase MOZ (monocytic leukemia zinc finger) have vital roles in transcriptional regulation and are implicated in aggressive forms of leukemia. Here, we describe the mechanistic basis for the intertwined association of ENL and MOZ. Genomic analysis shows that ENL and MOZ co-occupy active promoters and that MOZ recruits ENL to its gene targets.
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