Report from the European Myeloma Network on interphase FISH in multiple myeloma and related disorders

Abstract

Home page: www.blodet.dkThe European Myeloma Network has organized two workshops on fluorescence in situ hybridization in multiple myeloma. The first aimed to identify specific indications and consensus technical approaches of current practice. A second workshop followed a quality control exercise in which 21 laboratories analyzed diagnostic cases of purified plasma cells for recurrent abnormalities. The summary report was discussed at the EHA Myeloma Scientific Working Group Meeting 2010. During the quality control exercise, there was acceptable agreement on more than 1,000 tests. The conclusions from the exercise were that the primary clinical applications for FISH analysis were for newly diagnosed cases of MM or frank relapse cases. A range of technical recommendations included: 1) material should be part of the first draw of the aspirate; 2) samples should be sent at suitable times to allow for the lengthy processing procedure; 3) most importantly, PCs must be purified or specifically identified; 4) positive cut-off levels should be relatively conservative: 10% for fusion or breakapart probes, 20% for numerical abnormalities; 5) informative probes should be combined to best effect; 6) in specialist laboratories, a single experienced analyst is considered adequate; 7) at least 100 PC should be scored; 8) essential abnormalities to test for are t(4;14), t(14;16) and 17p13 deletions; 9) suitable commercial probes should be available for clinically relevant abnormalities; 10) the clinical report should be expressed clearly and must state the percentage of PC involved and the method used for identification; 11) a retrospective European based FISH data bank linked to clinical data should be generated; and 12) prospective analysis should be centralized for upcoming trials based on the recommendations made. The European Myeloma Network aims to build on these recommendations to establish standards for a common European data base to define subgroups with prognostic significance.Key words: myeloma, cytogenetic, interphase FISH, recommendation.Citation: Ross FM, Avet-Loiseau H, Ameye G, Gutiérrez NC, Liebisch P, O´Connor S, Dalva K, Fabris S, Testi AM, Jarosova M, Hodkinson C, Collin A, Kerndrup G, Kuglik P, Ladon D, Bernasconi P, Maes B, Zemanova Z, Michalova K, Michau L, Neben K, Hermansen NEU, Rack K, Rocci A, Protheroe R, Chiecchio L, Poirel HA, Sonneveld P, Nyegaard M, and myeloma and related disorders. Haematologica 2012;97(8):1272-1277. doi:10.3324/haematol.2011 This is an open-access paper. ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n

Chromosome 1q21 gains confer inferior outcomes in multiple myeloma treated with bortezomib but copy number variation and percentage of plasma cells involved have no additional prognostic value

“…Where laboratories had used more than one probe, the results confirmed that the majority of abnormalities are gain of the whole arm. 8 Using sequential gene GEP samples, Zhan et al defined a major functional gene group related to bortezomib resistance, and several genes, such as NEK2, FAM72A, Nuf2, CDC20, were located at chromosome 1q.24 All these findings support the important role of chromosome 1q in drug resistance to bortezomib.…”

“…8 Because the prognostic value of the percentage of clones carrying cytogenetic aberration has rarely been investigated, there is still not enough evidence to determine the level that is of highest prognostic significance. In one study, del(17p) was not prognostic in all patients, and patients presenting del(17p) in less than 60% of their plasma cells did not have a specific poor outcome.…”

“…3 A total of 200 interphase nuclei were analyzed and the cut-off level was set at 20%. 8 The gains of 1q21 were divided into three categories based on copy numbers as follows: 1) three copies of 1q21 (the cells with at least four copies were seen in less than 20% of clonal plasma cells); 2) four copies of 1q21 (the cells with at least five copies were seen in less than 20% of clonal plasma cells); and 3) at least five copies of 1q21 (the cells with at least five copies were seen in at least 20% of clonal plasma cells). 3 …”

“…for deletions and numerical aberrations the cut-off level was set at 20%. 8 In one report, del(17p) is prognostic only if present in at least 60% of the plasma cells. 9 However, in studies from Neben et al,del(17p) remains the most important genetic prognostic factor in MM even if the proportion of plasma cells involved is just over 10%.…”

Understanding the multiple biological aspects leading to myeloma

“…79 In myeloma, its loss is associated with a significantly more aggressive disease phenotype 80,81 and disease progression. 82 Mutations occurring at a low frequency have also been described. 74,83 Editorials and Perspectives haematologica | 2014; 99 (4) 607…”