Genomic Imbalances Are Confined to Non-Proliferating Cells in Paediatric Patients with Acute Myeloid Leukaemia and a Normal or Incomplete Karyotype

Leukaemia is often associated with genetic alterations such as translocations, amplifications and deletions, and recurrent chromosome abnormalities are used as markers of diagnostic and prognostic relevance. However, a proportion of acute myeloid leukaemia (AML) cases have an apparently normal karyo...

Full description

Bibliographic Details
Main Authors:	Ballabio, Erica, Regan, Regina, Garimberti, Elisa, Harbott, Jochen, Bradtke, Jutta, Teigler-Schlegel, Andrea, Biondi, Andrea, Cazzaniga, Giovanni, Giudici, Giovanni, Wainscoat, James S., Boultwood, Jacqueline, Bridger, Joanna M., Knight, Samantha J. L., Tosi, Sabrina
Format:	Online
Language:	English
Published:	Public Library of Science 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111408/

id	pubmed-3111408
recordtype	oai_dc
spelling	pubmed-31114082011-06-21 Genomic Imbalances Are Confined to Non-Proliferating Cells in Paediatric Patients with Acute Myeloid Leukaemia and a Normal or Incomplete Karyotype Ballabio, Erica Regan, Regina Garimberti, Elisa Harbott, Jochen Bradtke, Jutta Teigler-Schlegel, Andrea Biondi, Andrea Cazzaniga, Giovanni Giudici, Giovanni Wainscoat, James S. Boultwood, Jacqueline Bridger, Joanna M. Knight, Samantha J. L. Tosi, Sabrina Research Article Leukaemia is often associated with genetic alterations such as translocations, amplifications and deletions, and recurrent chromosome abnormalities are used as markers of diagnostic and prognostic relevance. However, a proportion of acute myeloid leukaemia (AML) cases have an apparently normal karyotype despite comprehensive cytogenetic analysis. Based on conventional cytogenetic analysis of banded chromosomes, we selected a series of 23 paediatric patients with acute myeloid leukaemia and performed whole genome array comparative genome hybridization (aCGH) using DNA samples derived from the same patients. Imbalances involving large chromosomal regions or entire chromosomes were detected by aCGH in seven of the patients studied. Results were validated by fluorescence in situ hybridization (FISH) to both interphase nuclei and metaphase chromosomes using appropriate bacterial artificial chromosome (BAC) probes. The majority of these copy number alterations (CNAs) were confirmed by FISH and found to localize to the interphase rather than metaphase nuclei. Furthermore, the proliferative states of the cells analyzed by FISH were tested by immunofluorescence using an antibody against the proliferation marker pKi67. Interestingly, these experiments showed that, in the vast majority of cases, the changes appeared to be confined to interphase nuclei in a non-proliferative status. Public Library of Science 2011-06-09 /pmc/articles/PMC3111408/ /pubmed/21694761 http://dx.doi.org/10.1371/journal.pone.0020607 Text en Ballabio et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Ballabio, Erica Regan, Regina Garimberti, Elisa Harbott, Jochen Bradtke, Jutta Teigler-Schlegel, Andrea Biondi, Andrea Cazzaniga, Giovanni Giudici, Giovanni Wainscoat, James S. Boultwood, Jacqueline Bridger, Joanna M. Knight, Samantha J. L. Tosi, Sabrina
spellingShingle	Ballabio, Erica Regan, Regina Garimberti, Elisa Harbott, Jochen Bradtke, Jutta Teigler-Schlegel, Andrea Biondi, Andrea Cazzaniga, Giovanni Giudici, Giovanni Wainscoat, James S. Boultwood, Jacqueline Bridger, Joanna M. Knight, Samantha J. L. Tosi, Sabrina Genomic Imbalances Are Confined to Non-Proliferating Cells in Paediatric Patients with Acute Myeloid Leukaemia and a Normal or Incomplete Karyotype
author_facet	Ballabio, Erica Regan, Regina Garimberti, Elisa Harbott, Jochen Bradtke, Jutta Teigler-Schlegel, Andrea Biondi, Andrea Cazzaniga, Giovanni Giudici, Giovanni Wainscoat, James S. Boultwood, Jacqueline Bridger, Joanna M. Knight, Samantha J. L. Tosi, Sabrina
author_sort	Ballabio, Erica
title	Genomic Imbalances Are Confined to Non-Proliferating Cells in Paediatric Patients with Acute Myeloid Leukaemia and a Normal or Incomplete Karyotype
title_short	Genomic Imbalances Are Confined to Non-Proliferating Cells in Paediatric Patients with Acute Myeloid Leukaemia and a Normal or Incomplete Karyotype
title_full	Genomic Imbalances Are Confined to Non-Proliferating Cells in Paediatric Patients with Acute Myeloid Leukaemia and a Normal or Incomplete Karyotype
title_fullStr	Genomic Imbalances Are Confined to Non-Proliferating Cells in Paediatric Patients with Acute Myeloid Leukaemia and a Normal or Incomplete Karyotype
title_full_unstemmed	Genomic Imbalances Are Confined to Non-Proliferating Cells in Paediatric Patients with Acute Myeloid Leukaemia and a Normal or Incomplete Karyotype
title_sort	genomic imbalances are confined to non-proliferating cells in paediatric patients with acute myeloid leukaemia and a normal or incomplete karyotype
description	Leukaemia is often associated with genetic alterations such as translocations, amplifications and deletions, and recurrent chromosome abnormalities are used as markers of diagnostic and prognostic relevance. However, a proportion of acute myeloid leukaemia (AML) cases have an apparently normal karyotype despite comprehensive cytogenetic analysis. Based on conventional cytogenetic analysis of banded chromosomes, we selected a series of 23 paediatric patients with acute myeloid leukaemia and performed whole genome array comparative genome hybridization (aCGH) using DNA samples derived from the same patients. Imbalances involving large chromosomal regions or entire chromosomes were detected by aCGH in seven of the patients studied. Results were validated by fluorescence in situ hybridization (FISH) to both interphase nuclei and metaphase chromosomes using appropriate bacterial artificial chromosome (BAC) probes. The majority of these copy number alterations (CNAs) were confirmed by FISH and found to localize to the interphase rather than metaphase nuclei. Furthermore, the proliferative states of the cells analyzed by FISH were tested by immunofluorescence using an antibody against the proliferation marker pKi67. Interestingly, these experiments showed that, in the vast majority of cases, the changes appeared to be confined to interphase nuclei in a non-proliferative status.
publisher	Public Library of Science
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111408/
_version_	1611458487778279424

Genomic Imbalances Are Confined to Non-Proliferating Cells in Paediatric Patients with Acute Myeloid Leukaemia and a Normal or Incomplete Karyotype

Similar Items