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Molecular similarity between myelodysplastic form of chronic myelomonocytic leukemia and refractory anemia with ring sideroblasts.

Molecular similarity between myelodysplastic form of chronic myelomonocytic leukemia and refractory anemia with ring sideroblasts.
Molecular similarity between myelodysplastic form of chronic myelomonocytic leukemia and refractory anemia with ring sideroblasts.
Background. Chronic myelomonocytic leukemia is close to, but separate from both myeloproliferative neoplasms and myelodysplastic syndromes, and shows either myeloproliferative or myelodysplastic features. We ask whether this distinction may have a molecular basis. Design and Methods. We established the gene expression profiles of 39 samples of chronic myelomonocytic leukemia (including 12 CD34-positive) and 32 CD34-positive samples of myelodysplastic syndromes by using Affymetrix microarrays, and studied the status of 18 genes by Sanger sequencing and array-comparative genomic hybridization in 53 samples. Results. Analysis of 12 mRNAS from chronic myelomonocytic leukemia established a gene expression signature of 122 probe sets differentially expressed between proliferative and dysplastic cases of chronic myelomonocytic leukemia. As compared to the former, the latter overexpressed genes involved in red blood cell biology. When applied to 32 myelodysplastic syndromes this gene expression signature was able to discriminate refractory anemias with ring sideroblasts from refractory anemias with excess of blasts. By comparing mRNAS from these two forms of myelodysplastic syndromes we derived a second gene expression signature. This signature separated the myelodysplastic and myeloproliferative forms of chronic myelomonocytic leukemias. These results were validated by using two independent gene expression data sets. We found that myelodysplastic chronic myelomonocytic leukemias are characterized by mutations in transcription/epigenetic regulators (ASXL1, RUNX1, TET2) and splicing genes (SRSF2) and the absence of mutations in signaling genes. Conclusions. Myelodysplastic chronic myelomonocytic leukemias and refractory anemias with ring sideroblasts share a common expression program suggesting they are part of a continuum, which is not totally explained by their similar but not identical mutation spectrum.
0390-6078
576-583
Gelsi-Boyer, Veronique
20723bb2-890e-439b-99fa-4d3a5305b46b
Cervera, Nathalie
1b5a8e30-17b9-443a-b32c-1ae892400b13
Bertucci, Francois
1cef6086-f0fa-47c3-a355-c5b3bf747071
Brecqueville, Mandy
2f99abe8-5061-4ee2-ae60-9741005a2f4c
Finetti, Pascal
16885ba4-5d97-4dbf-b728-a512bfa913d2
Murati, Anne
ed52b08d-76e3-4810-a96a-18a6030b03ec
Arnoulet, Christine
34ba9a18-cdf2-4382-b75e-c386454cd5ce
Mozziconacci, Marie-Joelle
14c9dd96-0fd0-4d1e-b72a-33981a844a88
Mills, Ken
d9e5594b-88de-480b-bc15-15b6bbe94a92
Cross, Nicholas C P
f87650da-b908-4a34-b31b-d62c5f186fe4
Vey, Norbert
4a4e2680-0963-4754-b334-d9a96037055f
Birnbaum, Daniel
3c44771b-e82f-4499-9779-7546d3e15fe1
Gelsi-Boyer, Veronique
20723bb2-890e-439b-99fa-4d3a5305b46b
Cervera, Nathalie
1b5a8e30-17b9-443a-b32c-1ae892400b13
Bertucci, Francois
1cef6086-f0fa-47c3-a355-c5b3bf747071
Brecqueville, Mandy
2f99abe8-5061-4ee2-ae60-9741005a2f4c
Finetti, Pascal
16885ba4-5d97-4dbf-b728-a512bfa913d2
Murati, Anne
ed52b08d-76e3-4810-a96a-18a6030b03ec
Arnoulet, Christine
34ba9a18-cdf2-4382-b75e-c386454cd5ce
Mozziconacci, Marie-Joelle
14c9dd96-0fd0-4d1e-b72a-33981a844a88
Mills, Ken
d9e5594b-88de-480b-bc15-15b6bbe94a92
Cross, Nicholas C P
f87650da-b908-4a34-b31b-d62c5f186fe4
Vey, Norbert
4a4e2680-0963-4754-b334-d9a96037055f
Birnbaum, Daniel
3c44771b-e82f-4499-9779-7546d3e15fe1

Gelsi-Boyer, Veronique, Cervera, Nathalie, Bertucci, Francois, Brecqueville, Mandy, Finetti, Pascal, Murati, Anne, Arnoulet, Christine, Mozziconacci, Marie-Joelle, Mills, Ken, Cross, Nicholas C P, Vey, Norbert and Birnbaum, Daniel (2013) Molecular similarity between myelodysplastic form of chronic myelomonocytic leukemia and refractory anemia with ring sideroblasts. Haematologica, 98 (4), 576-583. (doi:10.3324/haematol.2012.071506). (PMID:23065512)

Record type: Article

Abstract

Background. Chronic myelomonocytic leukemia is close to, but separate from both myeloproliferative neoplasms and myelodysplastic syndromes, and shows either myeloproliferative or myelodysplastic features. We ask whether this distinction may have a molecular basis. Design and Methods. We established the gene expression profiles of 39 samples of chronic myelomonocytic leukemia (including 12 CD34-positive) and 32 CD34-positive samples of myelodysplastic syndromes by using Affymetrix microarrays, and studied the status of 18 genes by Sanger sequencing and array-comparative genomic hybridization in 53 samples. Results. Analysis of 12 mRNAS from chronic myelomonocytic leukemia established a gene expression signature of 122 probe sets differentially expressed between proliferative and dysplastic cases of chronic myelomonocytic leukemia. As compared to the former, the latter overexpressed genes involved in red blood cell biology. When applied to 32 myelodysplastic syndromes this gene expression signature was able to discriminate refractory anemias with ring sideroblasts from refractory anemias with excess of blasts. By comparing mRNAS from these two forms of myelodysplastic syndromes we derived a second gene expression signature. This signature separated the myelodysplastic and myeloproliferative forms of chronic myelomonocytic leukemias. These results were validated by using two independent gene expression data sets. We found that myelodysplastic chronic myelomonocytic leukemias are characterized by mutations in transcription/epigenetic regulators (ASXL1, RUNX1, TET2) and splicing genes (SRSF2) and the absence of mutations in signaling genes. Conclusions. Myelodysplastic chronic myelomonocytic leukemias and refractory anemias with ring sideroblasts share a common expression program suggesting they are part of a continuum, which is not totally explained by their similar but not identical mutation spectrum.

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Accepted/In Press date: 12 October 2012
Published date: April 2013
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 344282
URI: http://eprints.soton.ac.uk/id/eprint/344282
ISSN: 0390-6078
PURE UUID: 9fcce231-1481-4001-b82a-989456c618c3
ORCID for Nicholas C P Cross: ORCID iD orcid.org/0000-0001-5481-2555

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Date deposited: 16 Oct 2012 14:16
Last modified: 08 Jan 2022 02:55

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Contributors

Author: Veronique Gelsi-Boyer
Author: Nathalie Cervera
Author: Francois Bertucci
Author: Mandy Brecqueville
Author: Pascal Finetti
Author: Anne Murati
Author: Christine Arnoulet
Author: Marie-Joelle Mozziconacci
Author: Ken Mills
Author: Norbert Vey
Author: Daniel Birnbaum

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