Objective: To investigate the expression of AML1/ETO9a isoform in the acute myeloid leukemia (AML)-M2 patients.
Methods: Expressions of AML1/ETO fusion gene and AML1/ETO9a isoform were detected by using reverse transcriptase-polymerase chain reaction (RT-PCR) in leukemia patients, MDS patients, leukemia cell lines and healthy subjects. Karyotype was studied by R-banding technique.
Result: In 30 newly diagnosed AML-M2 patients 15 were found to express AML1/ETO9a isoform, while the rest including 20 AML-M2CR, 18 other subtypes of AML, 5 chronic myelogenous leukemia (CML), 3 myelodysplastic syndromes (MDS), 3 leukemia cell lines (NB4, KG-1, K562) and 5 healthy subjects were AML1/ETO9a negative. Among the 15 AML/ETO9a isoform expressing cases, 13 were demonstrated t(8;21) translocation and AML1/ETO expression.
Conclusion: Isoform AML1/ETO9a was correlated to AML/M2, and it may promote the development of leukemia in combination with the AML1/ETO fusion gene.
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Leukemia
February 2020
Klinik für Innere Medizin I, Universitätsklinikum Ulm, Ulm, Germany.
Ann Hematol
January 2019
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya, 466-8550, Japan.
We analyzed the clinical significance and genetic features of ASXL2 and ZBTB7A mutations, and the alternatively spliced isoform of the RUNX1-RUNX1T1 transcript, which is also called AML1-ETO9a (AE9a), in Japanese CBF-AML patients enrolled in the JALSG AML201 study. ASXL2 and ZBTB7A genes were sequenced using bone marrow samples of 41 AML patients with t(8;21) and 14 with inv(16). The relative expression levels of AE9a were quantified using the real-time PCR assay in 23 AML patients with t(8;21).
View Article and Find Full Text PDFPLoS Genet
January 2016
Cancer Research UK Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, United Kingdom.
The Core Binding Factor (CBF) protein RUNX1 is a master regulator of definitive hematopoiesis, crucial for hematopoietic stem cell (HSC) emergence during ontogeny. RUNX1 also plays vital roles in adult mice, in regulating the correct specification of numerous blood lineages. Akin to the other mammalian Runx genes, Runx1 has two promoters P1 (distal) and P2 (proximal) which generate distinct protein isoforms.
View Article and Find Full Text PDFBlood
October 2015
Department of Medicine, University of Chicago, Chicago, IL; Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH;
It is generally assumed that gain- and loss-of-function manipulations of a functionally important gene should lead to the opposite phenotypes. We show in this study that both overexpression and knockout of microRNA (miR)-126 surprisingly result in enhanced leukemogenesis in cooperation with the t(8;21) fusion genes AML1-ETO/RUNX1-RUNX1T1 and AML1-ETO9a (a potent oncogenic isoform of AML1-ETO). In accordance with our observation that increased expression of miR-126 is associated with unfavorable survival in patients with t(8;21) acute myeloid leukemia (AML), we show that miR-126 overexpression exhibits a stronger effect on long-term survival and progression of AML1-ETO9a-mediated leukemia stem cells/leukemia initiating cells (LSCs/LICs) in mice than does miR-126 knockout.
View Article and Find Full Text PDFZhonghua Xue Ye Xue Za Zhi
January 2012
The First Affiliated Hospital of Soochow University, Suzhou, China.
Objective: To study the expression ratio of AML1-ETO9a (AE9a) isoform in t(8;21) acute myeloid leukemia (AML) and its clinical significance.
Methods: Bone marrow samples from 44 newly diagnosed t(8;21) AML patients co-expressed AE9a and AE were screened by RT-PCR. The alteration of the AE9a expression ratio was monitored during follow-up by using quantitative real-time RT-PCR (qPCR).
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