Deletions of the derivative chromosome 9 occur at the time of the Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia.

2.50
Hdl Handle:
http://hdl.handle.net/10541/83240
Title:
Deletions of the derivative chromosome 9 occur at the time of the Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia.
Authors:
Huntly, B J; Reid, A G; Bench, A J; Campbell, L J; Telford, Nicholas; Shepherd, P; Szer, J; Prince, H M; Turner, P; Grace, C; Nacheva, E P; Green, Anthony R
Abstract:
Chronic myeloid leukemia (CML) is characterized by formation of the BCR-ABL fusion gene, usually as a consequence of the Philadelphia (Ph) translocation between chromosomes 9 and 22. Large deletions on the derivative chromosome 9 have recently been reported, but it was unclear whether deletions arose during disease progression or at the time of the Ph translocation. Fluorescence in situ hybridization (FISH) analysis was used to assess the deletion status of 253 patients with CML. The strength of deletion status as a prognostic indicator was then compared to the Sokal and Hasford scoring systems. The frequency of deletions was similar at diagnosis and after disease progression but was significantly increased in patients with variant Ph translocations. In patients with a deletion, all Ph(+) metaphases carried the deletion. The median survival of patients with and without deletions was 38 months and 88 months, respectively (P =.0001). By contrast the survival difference between Sokal or Hasford high-risk and non-high-risk patients was of only borderline significance (P =.057 and P =.034). The results indicate that deletions occur at the time of the Ph translocation. An apparently simple reciprocal translocation may therefore result in considerable genetic heterogeneity ab initio, a concept that is likely to apply to other malignancies associated with translocations. Deletion status is also a powerful and independent prognostic factor for patients with CML. The prognostic significance of deletion status should now be studied prospectively and, if confirmed, should be incorporated into management decisions and the analysis of clinical trials.
Affiliation:
Department of Hematology, University of Cambridge, Cambridge, United Kingdom.
Citation:
Deletions of the derivative chromosome 9 occur at the time of the Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia. 2001, 98 (6):1732-8 Blood
Journal:
Blood
Issue Date:
15-Sep-2001
URI:
http://hdl.handle.net/10541/83240
PubMed ID:
11535505
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorHuntly, B J-
dc.contributor.authorReid, A G-
dc.contributor.authorBench, A J-
dc.contributor.authorCampbell, L J-
dc.contributor.authorTelford, Nicholas-
dc.contributor.authorShepherd, P-
dc.contributor.authorSzer, J-
dc.contributor.authorPrince, H M-
dc.contributor.authorTurner, P-
dc.contributor.authorGrace, C-
dc.contributor.authorNacheva, E P-
dc.contributor.authorGreen, Anthony R-
dc.date.accessioned2009-10-01T14:11:09Z-
dc.date.available2009-10-01T14:11:09Z-
dc.date.issued2001-09-15-
dc.identifier.citationDeletions of the derivative chromosome 9 occur at the time of the Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia. 2001, 98 (6):1732-8 Blooden
dc.identifier.issn0006-4971-
dc.identifier.pmid11535505-
dc.identifier.urihttp://hdl.handle.net/10541/83240-
dc.description.abstractChronic myeloid leukemia (CML) is characterized by formation of the BCR-ABL fusion gene, usually as a consequence of the Philadelphia (Ph) translocation between chromosomes 9 and 22. Large deletions on the derivative chromosome 9 have recently been reported, but it was unclear whether deletions arose during disease progression or at the time of the Ph translocation. Fluorescence in situ hybridization (FISH) analysis was used to assess the deletion status of 253 patients with CML. The strength of deletion status as a prognostic indicator was then compared to the Sokal and Hasford scoring systems. The frequency of deletions was similar at diagnosis and after disease progression but was significantly increased in patients with variant Ph translocations. In patients with a deletion, all Ph(+) metaphases carried the deletion. The median survival of patients with and without deletions was 38 months and 88 months, respectively (P =.0001). By contrast the survival difference between Sokal or Hasford high-risk and non-high-risk patients was of only borderline significance (P =.057 and P =.034). The results indicate that deletions occur at the time of the Ph translocation. An apparently simple reciprocal translocation may therefore result in considerable genetic heterogeneity ab initio, a concept that is likely to apply to other malignancies associated with translocations. Deletion status is also a powerful and independent prognostic factor for patients with CML. The prognostic significance of deletion status should now be studied prospectively and, if confirmed, should be incorporated into management decisions and the analysis of clinical trials.en
dc.language.isoenen
dc.subjectMyeloid Leukaemiaen
dc.subject.meshAdult-
dc.subject.meshChromosome Deletion-
dc.subject.meshChromosomes, Human, Pair 9-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshIn Situ Hybridization, Fluorescence-
dc.subject.meshLeukemia, Myelogenous, Chronic, BCR-ABL Positive-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshPhiladelphia Chromosome-
dc.subject.meshPrognosis-
dc.subject.meshSurvival Rate-
dc.titleDeletions of the derivative chromosome 9 occur at the time of the Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia.en
dc.typeArticleen
dc.contributor.departmentDepartment of Hematology, University of Cambridge, Cambridge, United Kingdom.en
dc.identifier.journalBlooden

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