Acute myeloid leukemia (AML) in adults is a heterogeneous malignant pathology with a globally unfavorable prognosis. The classification of AML allows identification of subgroups with favorable prognosis. However, besides these specific subgroups, most patients will have an intermediate or unfavorable prognosis often resulting in induction failure, probably due to drug resistance of the leukemic blasts, and more frequently resulting in early relapse after achieving complete remission. This unfavorable situation leads to a strong need to develop new diagnostic and therapeutic options. However, development of these therapies and their efficient use requires a better understanding of the biology and the molecular pathogenesis of AML. Pharmacogenomics focuses on the genetic variation of drug-metabolizing enzymes, targets and transporters, and how these genetic variations interact to produce specific drug-related phenotypes. Potential genetic markers may serve to functionally subclassify patients by their disease and therefore influence the nature and intensity of treatment. This review summarizes important aspects of and recent advances in the field of pharmacogenomics in AML.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.2217/pgs.09.130 | DOI Listing |
Acute Myeloid Leukemia (AML) is an aggressive cancer with dismal outcomes, vast subtype heterogeneity, and suboptimal risk stratification. In this study, we harmonized DNA methylation data from 3,314 patients across 11 cohorts to develop the Acute Leukemia Methylome Atlas (ALMA) of diagnostic relevance that predicted 27 WHO 2022 acute leukemia subtypes with an overall accuracy of 96.3% in discovery and 90.
View Article and Find Full Text PDFAdoptive cell therapy (ACT) can address an unmet clinical need for patients with relapsed/refractory acute myeloid leukemia (AML), but its effect is often modest in the setting of high tumor burden. In this study, we postulated that strategies to lower the AML apoptotic threshold will augment T cell killing of AML cells. BH3 mimetics, such as venetoclax, are a clinically approved class of compounds that predispose cells to intrinsic apoptosis by inhibiting anti-apoptotic mitochondrial proteins.
View Article and Find Full Text PDFArch Pathol Lab Med
December 2024
From the Department of Hematopathology, University of Texas, MD Anderson Cancer Center, Houston.
Context.—: Blasts in myelodysplastic syndromes (MDSs) typically have a primitive myeloid immunophenotype (CD34+CD117+CD13+CD33+HLA-DR+). On rare occasions, blasts were found to be CD34 negative or minimally expressed in a presumptive MDS.
View Article and Find Full Text PDFACS Appl Mater Interfaces
December 2024
Epigenetics Research Laboratory, Institute of Nano Science and Technology, Knowledge City, Sector 81, Mohali, Punjab 140306, India.
The heterogeneous form of malignancy in the myeloid lineage of normal hematopoietic stem cells (HSCs) is characterized as acute myeloid leukemia (AML). The t(9;11) reciprocal translocation (p22;q23) generates MLL-AF9 oncogene, which results in myeloid-based monoblastic AML with frequent relapse and poor survival. MLL-AF9 binds with the C-Myb promoter and regulates AML onset, maintenance, and survival.
View Article and Find Full Text PDFBr J Haematol
December 2024
Hospital of University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Outcomes of myeloproliferative neoplasms (MPN)-associated acute leukaemias are dismal with conventional therapy. Approximately 20% of MPN-associated acute leukaemias have mutations in isocitrate dehydrogenase (IDH). Olutasidenib, and inhibitor of IDH1, demonstrates important clinical benefits in MPN-associated leukaemia with IDH1 mutation.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!