Association of the type of 5q loss with complex karyotype, clonal evolution, TP53 mutation status, and prognosis in acute myeloid leukemia and myelodysplastic syndrome. Issue 5 (3rd February 2014)

• Record Type: Journal Article
• Authors: Volkert, Sarah; Kohlmann, Alexander; Schnittger, Susanne; Kern, Wolfgang; Haferlach, Torsten; Haferlach, Claudia
• Is Part Of: Genes, chromosomes & cancer. Volume 53:Issue 5(2014:May)
• Page Start: 402
• Page End: 410
• Publication Date: 2014-02-03
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22151
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>We analyzed 1, 200 patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) harboring a 5q deletion in order to clarify whether the type of 5q loss is associated with other biological markers and prognosis. We investigated all patients by chromosome banding analysis, FISH with a probe for <italic>EGR1</italic> (5q31) and, if necessary, to resolve complex karyotypes with 24‐color‐FISH. Moreover, 420 patients were analyzed for mutations in the <italic>TP53</italic> gene. The patient cohort was subdivided based on type of 5q loss: Patients with interstitial deletions and patients with 5q loss due to unbalanced rearrangements or monosomy 5. Loss of the long arm of chromosome 5 due to an unbalanced rearrangement occurred more often in AML (286/627; 45.6%) than MDS (188/573; 32.8%; <italic>P</italic> < 0.001). In both entities, patients with 5q loss due to unbalanced translocations showed complex karyotypes more frequently (MDS: 179/188; 95.2% vs. 124/385; 32.2%; <italic>P</italic> < 0.001; AML: 274/286; 95.8% vs. 256/341; 75.1%; <italic>P</italic> < 0.001). Moreover, in MDS unbalanced 5q translocations were associated with clonal evolution (109/188; 58.0% vs. 124/385; 32.2%; <italic>P</italic> < 0.001), mutation of <italic>TP53</italic> (64/67; 95.5% vs. 40/120; 40.0%; <italic>P</italic> < 0.001), and shorter survival (15.3 months vs. not reached; <italic>P</italic> < 0.001). In MDS, complex karyotype was an independent adverse prognostic factor (HR = 5.34; <italic>P</italic> = 0.032), whereas in AML presence of <italic>TP53</italic> mutations was the strongest adverse prognostic factor (HR = 2.21; <italic>P</italic> = 0.026). In conclusion, in AML and MDS, loss of the long arm of chromosome 5 due to unbalanced translocations is associated with complex karyotype and in MDS, moreover, with clonal evolution, mutations in the <italic>TP53</italic> gene and adverse prognosis. © 2014 Wiley Periodicals, Inc.</p> </abstract>