Heterozygous deletion of the PU.1 locus in human AML

Bonadies, Nicola; Pabst, Thomas; Mueller, Beatrice U (2010). Heterozygous deletion of the PU.1 locus in human AML. Blood, 115(2), pp. 331-4. Washington, D.C.: American Society of Hematology 10.1182/blood-2009-03-212225

Full text not available from this repository. (Request a copy)

The transcription factor PU.1 is essential for myeloid development. Targeted disruption of an upstream regulatory element (URE) decreases PU.1 expression by 80% and leads to acute myeloid leukemia (AML) in mice. Here, we sequenced the URE sequences of PU.1 in 120 AML patients. Four polymorphisms (single nucleotide polymorphisms [SNPs]) in the URE were observed, with homozygosity in all SNPs in 37 patients. Among them, we compared samples at diagnosis and remission, and one patient with cytogenetically normal acute myeloid leukemia M2 was identified with heterozygosity in 3 of the SNPs in the URE at remission. Loss of heterozygosity was further found in this patient at 2 polymorphic sites in the 5' promoter region and in 2 intronic sites flanking exon 4, thus suggesting loss of heterozygosity covering at least 40 kb of the PU.1 locus. Consistently, PU.1 expression in this patient was markedly reduced. Our study suggests that heterozygous deletion of the PU.1 locus can be associated with human AML.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine > Centre of Competence for General Internal Medicine
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Bonadies, Nicola; Pabst, Thomas and Müller, Beatrice Ursula

ISSN:

0006-4971

Publisher:

American Society of Hematology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:07

Last Modified:

04 May 2014 23:04

Publisher DOI:

10.1182/blood-2009-03-212225

PubMed ID:

19890096

Web of Science ID:

000273622600025

URI:

https://boris.unibe.ch/id/eprint/101 (FactScience: 195878)

Actions (login required)

Edit item Edit item
Provide Feedback