Ploidy, as detected by fluorescence in situ hybridization, defines different subgroups in multiple myeloma

Wuillème, Soraya; Robillard, Nelly; Lodé, Laurence; Magrangeas, Florence; Beris, Helen; Harousseau, J L; Proffitt, J H; Minvielle, Stéphane; Avet-Loiseau, Hervé

doi:10.1038/sj.leu.2403586

Cited by 110 publications

(118 citation statements)

References 24 publications

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“…Analyses were performed on CD138-purified plasma cells 18 and the presence of clonal/subclonal aberrations as well as the absolute number of chromosomal aberrations present were defined as described. 30 The score of Wuilleme et al 31 was used to assess ploidy. The percentage of malignant plasma cells was surrogated by the highest percentage of all tested chromosomal aberrations within this sample.…”

Section: Interphase Fluorescence In Situ Hybridizationmentioning

confidence: 99%

Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma

Hose

Rème²,

Hielscher³

et al. 2010

Haematologica

195

196

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BackgroundProliferation of malignant plasma cells is a strong adverse prognostic factor in multiple myeloma and simultaneously targetable by available (e.g. tubulin polymerase inhibitors) and upcoming (e.g. aurora kinase inhibitors) compounds. Design and MethodsWe assessed proliferation using gene expression-based indices in 757 samples including independent cohorts of 298 and 345 samples of CD138-purified myeloma cells from previously untreated patients undergoing high-dose chemotherapy, together with clinical prognostic factors, chromosomal aberrations, and gene expression-based high-risk scores. ResultsIn the two cohorts, 43.3% and 39.4% of the myeloma cell samples showed a proliferation index above the median plus three standard deviations of normal bone marrow plasma cells. Malignant plasma cells of patients in advanced stages or those harboring disease progressionassociated gain of 1q21 or deletion of 13q14.3 showed significantly higher proliferation indices; patients with gain of chromosome 9, 15 or 19 (hyperdiploid samples) had significantly lower proliferation indices. Proliferation correlated with the presence of chromosomal aberrations in metaphase cytogenetics. It was significantly predictive for event-free and overall survival in both cohorts, allowed highly predictive risk stratification (e.g. event-free survival 12.7 versus 26.2 versus 40.6 months, P<0.001) of patients, and was largely independent of clinical prognostic factors, e.g. serum β2-microglobulin, International Staging System stage, associated high-risk chromosomal aberrations, e.g. translocation t(4;14), and gene expression-based high-risk scores. ConclusionsProliferation assessed by gene expression profiling, being independent of serum-β2-microglobulin, International Staging System stage, t(4;14), and gene expression-based risk scores, is a central prognostic factor in multiple myeloma. Surrogating a biological targetable variable, gene expression-based assessment of proliferation allows selection of patients for riskadapted anti-proliferative treatment on the background of conventional and gene expressionbased risk factors.

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Section: Interphase Fluorescence In Situ Hybridizationmentioning

confidence: 99%

Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma

Hose

Rème²,

Hielscher³

et al. 2010

Haematologica

195

196

View full text Add to dashboard Cite

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“…18,[30][31][32]39,48,49 All studies to date have shown superiority in overall survival and progression-free survival for patients with hyperdiploidy, whether this is detected by flow cytometry determination of DNA content, karyotype analysis [50][51][52] or gene expression profile. 6,39,53 In a recent publication, we were able to show that this difference in survival was not clearly related to initial responsiveness to treatment (using melphalan based strategies); thus, the difference in outcomes reflects a prolonged remission duration.…”

Section: Genetic Features Of Low-risk Disease T(11;14) and T(6;14) Ismentioning

confidence: 99%

A practical guide to defining high-risk myeloma for clinical trials, patient counseling and choice of therapy

et al. 2007

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Clinical outcomes for multiple myeloma (MM) are highly heterogeneous and it is now clear that pivotal genetic events are the primary harbingers of such variation. These findings have broad implications for counseling, choice of therapy and the design and interpretation of clinical investigation. Indeed, as in acute leukemias and non-hodgkins lymphoma, we believe it is no longer acceptable to consider MM a single disease entity. As such, the accurate diagnosis of MM subtypes and the adoption of common criteria for the identification and stratification of MM patients has become critical. Herein, we provide a consensus high-risk definition and offer practical guidelines for the adoption of routine diagnostic testing. Although acknowledging that more refined classifications will continue to be developed, we propose that the definition of high-risk disease (any of the t(4;14), t(14;16), t(14;20), deletion 17q13, aneuploidy or deletion chromosome 13 by metaphase cytogenetics, or plasma cell labeling index 43.0) be adopted. This classification will identify most of the 25% of MM patients for whom current therapies are inadequate and for whom investigational regimens should be vigorously pursued. Conversely, the 75% of patients remaining have more favorable outcomes using existing -albeit non-curative -therapeutic options.

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“…Ploidy was assessed using a modification of the method of Wuilleme et al 20 All patients with an extra copy of probes for any two of chromosomes 5, 9 or 15 were defined as HRD. Cases not meeting these criteria but only showing loss of signals were defined as non-HRD, along with those having X4 copies of X4 probes (near tetraploidy, considered with non-HRD class 21 ).…”

Section: Ploidy Classification By Ifishmentioning

confidence: 99%

Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma

et al. 2006

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In myeloma, the prognostic impact of different strategies used to detect chromosome 13 deletion (D13) remains controversial. To address this, we compared conventional cytogenetics and interphase fluorescence in situ hybridization (iFISH) in a large multicenter study (n ¼ 794). The ability to obtain abnormal metaphases was associated with a poor prognosis, which was worse if D13, p53 deletion or t(4;14) was present, but only D13 remained significant on multivariate analysis. Patients with D13, by either cytogenetics or iFISH, had a poor prognosis. However, when cases with D13 detectable by both cytogenetics and iFISH were separated from those detected by iFISH only, the poor prognosis of iFISH-detectable D13 disappeared; their outcome matched that of patients with no detectable D13 (P ¼ 0.115). Addition of ploidy status to iFISH-D13 did not affect the prognostic value of the test. Indeed both cytogenetics and iFISH D13 divided both hyperdiploidy and nonhyperdiploidy into two groups with similar prognoses, indicating that the poor prognosis of ploidy is entirely due to its association with D13. We conclude that D13 detected by metaphase analysis is a critical prognostic factor in myeloma. Absence of D13, even in those patients yielding only normal or no metaphases, is associated with a relatively good prognosis.

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Ploidy, as detected by fluorescence in situ hybridization, defines different subgroups in multiple myeloma

Cited by 110 publications

References 24 publications

Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma

Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma

A practical guide to defining high-risk myeloma for clinical trials, patient counseling and choice of therapy

Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma

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