miR-3151 interplays with its host gene BAALC and independently affects outcome of patients with cytogenetically normal acute myeloid leukemia

High BAALC expression levels are associated with poor outcome in cytogenetically normal acute myeloid leukemia (CN-AML) patients. Recently, miR-3151 was discovered in intron 1 of BAALC. To evaluate the prognostic significance of miR-3151 expression levels and to gain insight into the biologic and pr...

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Veröffentlicht in:Blood 2012-07, Vol.120 (2), p.249-258
Hauptverfasser: Eisfeld, Ann-Kathrin, Marcucci, Guido, Maharry, Kati, Schwind, Sebastian, Radmacher, Michael D., Nicolet, Deedra, Becker, Heiko, Mrózek, Krzysztof, Whitman, Susan P., Metzeler, Klaus H., Mendler, Jason H., Wu, Yue-Zhong, Liyanarachchi, Sandya, Patel, Ravi, Baer, Maria R., Powell, Bayard L., Carter, Thomas H., Moore, Joseph O., Kolitz, Jonathan E., Wetzler, Meir, Caligiuri, Michael A., Larson, Richard A., Tanner, Stephan M., de la Chapelle, Albert, Bloomfield, Clara D.
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container_end_page 258
container_issue 2
container_start_page 249
container_title Blood
container_volume 120
creator Eisfeld, Ann-Kathrin
Marcucci, Guido
Maharry, Kati
Schwind, Sebastian
Radmacher, Michael D.
Nicolet, Deedra
Becker, Heiko
Mrózek, Krzysztof
Whitman, Susan P.
Metzeler, Klaus H.
Mendler, Jason H.
Wu, Yue-Zhong
Liyanarachchi, Sandya
Patel, Ravi
Baer, Maria R.
Powell, Bayard L.
Carter, Thomas H.
Moore, Joseph O.
Kolitz, Jonathan E.
Wetzler, Meir
Caligiuri, Michael A.
Larson, Richard A.
Tanner, Stephan M.
de la Chapelle, Albert
Bloomfield, Clara D.
description High BAALC expression levels are associated with poor outcome in cytogenetically normal acute myeloid leukemia (CN-AML) patients. Recently, miR-3151 was discovered in intron 1 of BAALC. To evaluate the prognostic significance of miR-3151 expression levels and to gain insight into the biologic and prognostic interplay between miR-3151 and its host, miR-3151 and BAALC expression were measured in pretreatment blood of 179 CN-AML patients. Gene-expression profiling and miRNA-expression profiling were performed using microarrays. High miR-3151 expression was associated with shorter disease-free and overall survival, whereas high BAALC expression predicted failure of complete remission and shorter overall survival. Patients exhibiting high expression of both miR-3151 and BAALC had worse outcome than patients expressing low levels of either gene or both genes. In gene-expression profiling, high miR-3151 expressers showed down-regulation of genes involved in transcriptional regulation, posttranslational modification, and cancer pathways. Two genes, FBXL20 and USP40, were validated as direct miR-3151 targets. The results of the present study show that high expression of miR-3151 is an independent prognosticator for poor outcome in CN-AML and affects different outcome end points than its host gene, BAALC. The combination of both markers identified a patient subset with the poorest outcome. This interplay between an intronic miR and its host may have important biologic implications.
doi_str_mv 10.1182/blood-2012-02-408492
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Recently, miR-3151 was discovered in intron 1 of BAALC. To evaluate the prognostic significance of miR-3151 expression levels and to gain insight into the biologic and prognostic interplay between miR-3151 and its host, miR-3151 and BAALC expression were measured in pretreatment blood of 179 CN-AML patients. Gene-expression profiling and miRNA-expression profiling were performed using microarrays. High miR-3151 expression was associated with shorter disease-free and overall survival, whereas high BAALC expression predicted failure of complete remission and shorter overall survival. Patients exhibiting high expression of both miR-3151 and BAALC had worse outcome than patients expressing low levels of either gene or both genes. In gene-expression profiling, high miR-3151 expressers showed down-regulation of genes involved in transcriptional regulation, posttranslational modification, and cancer pathways. Two genes, FBXL20 and USP40, were validated as direct miR-3151 targets. The results of the present study show that high expression of miR-3151 is an independent prognosticator for poor outcome in CN-AML and affects different outcome end points than its host gene, BAALC. The combination of both markers identified a patient subset with the poorest outcome. This interplay between an intronic miR and its host may have important biologic implications.</description><identifier>ISSN: 0006-4971</identifier><identifier>ISSN: 1528-0020</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2012-02-408492</identifier><identifier>PMID: 22529287</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Aged ; Aged, 80 and over ; Biological and medical sciences ; Cytogenetic Analysis ; Disease-Free Survival ; F-Box Proteins - genetics ; Female ; Gene Expression ; Hematologic and hematopoietic diseases ; Humans ; Kaplan-Meier Estimate ; Leukemia, Myeloid, Acute - genetics ; Leukemias. 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subjects Aged
Aged, 80 and over
Biological and medical sciences
Cytogenetic Analysis
Disease-Free Survival
F-Box Proteins - genetics
Female
Gene Expression
Hematologic and hematopoietic diseases
Humans
Kaplan-Meier Estimate
Leukemia, Myeloid, Acute - genetics
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Male
Medical sciences
MicroRNAs - genetics
Middle Aged
Myeloid Neoplasia
Neoplasm Proteins - genetics
Plenary Paper
Prognosis
RNA, Neoplasm - genetics
Ubiquitin Thiolesterase - genetics
title miR-3151 interplays with its host gene BAALC and independently affects outcome of patients with cytogenetically normal acute myeloid leukemia
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