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Frequent upregulation of MYC in plasma cell leukemia

Frequent upregulation of MYC in plasma cell leukemia
Frequent upregulation of MYC in plasma cell leukemia
Plasma cell leukemia (PCL) is a rare form of monoclonal gammopathy, which can originate de novo or evolve from multiple myeloma (MM) as a terminal leukemic phase. Previous cytogenetic studies of PCL have reported the presence of complex karyotypes with involvement of multiple unidentified chromosomal regions. We report here the analysis of 12 PCL (10 primary and two secondary) by metaphase and FISH analysis combined with oligonucleotide array data (244 k, Agilent). Interphase-FISH results were compared with those from a series of 861 newly diagnosed patients with MM. Cytogenetic analysis was successful on 11 patients, all of whom showed clonal chromosomal abnormalities. Compared with MM, t(11;14)(q13;q32) (42% versus 15%; P = 0.027) and t(14;16)(q32;q23) (25% versus 4%; P = 0.010) were more frequent in PCL, although neither the specific partner chromosome involved in the IgH translocation nor the ploidy status predicted for survival. Chromosomes 1, 8, 13, and 16 showed the highest number of copy number alterations with 8q24 being the chromosomal region most frequently involved. In eight of 12 patients we found abnormalities (translocations, one amplification, small deletions, and duplications) that directly targeted or were very close to MYC. Only four of these changes were detected by routine FISH analysis using commercial probes with the others exclusively detected by arrays. Quantitative reverse transcription polymerase chain reaction demonstrated that these different abnormalities were associated with increased levels of MYC mRNA. We conclude that MYC dysregulation by complex mechanisms is one of the major molecular events in the oncogenesis of PCL
1045-2257
624-636
Chiecchio, Laura
3d2f63e3-3df1-4655-8478-00ecd89d009c
Dagrada, Gian Paolo
a6e0f6d8-2aa8-4cda-a595-7d75bc5cacf8
White, Helen E.
2181c0b9-fc3b-407e-95eb-3510524603e5
Townsend, Mark R.
08e4f0af-4360-402b-a3a3-a96a31f7918d
Protheroe, Rebecca K.M.
b2c9973f-ccf1-44a4-8e37-e76ee7e8ec0b
Cheung, Kan Luk
110c6d4d-6f0d-4c96-b207-071dace288d3
Stockley, David M.
fd8e48fa-cd20-4326-8608-795fb84cfda4
Orchard, Kim H.
794654ab-d6cc-488a-ac11-c9217433c7a2
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Harrison, Christine J.
52da7673-509c-4b88-b92e-0c021c9c7d3e
Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
UK Myloma Forum
Chiecchio, Laura
3d2f63e3-3df1-4655-8478-00ecd89d009c
Dagrada, Gian Paolo
a6e0f6d8-2aa8-4cda-a595-7d75bc5cacf8
White, Helen E.
2181c0b9-fc3b-407e-95eb-3510524603e5
Townsend, Mark R.
08e4f0af-4360-402b-a3a3-a96a31f7918d
Protheroe, Rebecca K.M.
b2c9973f-ccf1-44a4-8e37-e76ee7e8ec0b
Cheung, Kan Luk
110c6d4d-6f0d-4c96-b207-071dace288d3
Stockley, David M.
fd8e48fa-cd20-4326-8608-795fb84cfda4
Orchard, Kim H.
794654ab-d6cc-488a-ac11-c9217433c7a2
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Harrison, Christine J.
52da7673-509c-4b88-b92e-0c021c9c7d3e
Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba

Chiecchio, Laura, Dagrada, Gian Paolo, White, Helen E., Townsend, Mark R., Protheroe, Rebecca K.M., Cheung, Kan Luk, Stockley, David M., Orchard, Kim H., Cross, Nicholas C.P., Harrison, Christine J. and Ross, Fiona M. , UK Myloma Forum (2009) Frequent upregulation of MYC in plasma cell leukemia. Genes, Chromosomes and Cancer, 48 (7), 624-636. (doi:10.1002/gcc.20670).

Record type: Article

Abstract

Plasma cell leukemia (PCL) is a rare form of monoclonal gammopathy, which can originate de novo or evolve from multiple myeloma (MM) as a terminal leukemic phase. Previous cytogenetic studies of PCL have reported the presence of complex karyotypes with involvement of multiple unidentified chromosomal regions. We report here the analysis of 12 PCL (10 primary and two secondary) by metaphase and FISH analysis combined with oligonucleotide array data (244 k, Agilent). Interphase-FISH results were compared with those from a series of 861 newly diagnosed patients with MM. Cytogenetic analysis was successful on 11 patients, all of whom showed clonal chromosomal abnormalities. Compared with MM, t(11;14)(q13;q32) (42% versus 15%; P = 0.027) and t(14;16)(q32;q23) (25% versus 4%; P = 0.010) were more frequent in PCL, although neither the specific partner chromosome involved in the IgH translocation nor the ploidy status predicted for survival. Chromosomes 1, 8, 13, and 16 showed the highest number of copy number alterations with 8q24 being the chromosomal region most frequently involved. In eight of 12 patients we found abnormalities (translocations, one amplification, small deletions, and duplications) that directly targeted or were very close to MYC. Only four of these changes were detected by routine FISH analysis using commercial probes with the others exclusively detected by arrays. Quantitative reverse transcription polymerase chain reaction demonstrated that these different abnormalities were associated with increased levels of MYC mRNA. We conclude that MYC dysregulation by complex mechanisms is one of the major molecular events in the oncogenesis of PCL

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Published date: July 2009
Organisations: Human Genetics

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Local EPrints ID: 69555
URI: https://eprints.soton.ac.uk/id/eprint/69555
ISSN: 1045-2257
PURE UUID: 16424152-39af-4c08-b4a5-502738382dc3
ORCID for Kim H. Orchard: ORCID iD orcid.org/0000-0003-2276-3925
ORCID for Nicholas C.P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

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Date deposited: 18 Nov 2009
Last modified: 06 Jun 2018 12:49

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Contributors

Author: Laura Chiecchio
Author: Gian Paolo Dagrada
Author: Helen E. White
Author: Mark R. Townsend
Author: Rebecca K.M. Protheroe
Author: Kan Luk Cheung
Author: David M. Stockley
Author: Kim H. Orchard ORCID iD
Author: Christine J. Harrison
Author: Fiona M. Ross

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