High detection rate of clinically relevant genomic abnormalities in plasma cells enriched from patients with multiple myeloma

Stevens‐Kroef, Marian; Weghuis, Daniël Olde; Croockewit, Sandra; Derksen, Leo; Hooijer, Jeroen D; ElIdrissi-Zaynoun, Najat; Siepman, Angelique; Simons, Annet; Kessel, Ad Geurts van

doi:10.1002/gcc.21982

Cited by 22 publications

(15 citation statements)

References 26 publications

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“…The chromothripsis-like pattern has been commonly observed in 1q, 13q, and 16q as compared to the chromothripsis-like pattern confirmed in this study and similar results in other studies [22, 45]. Unlike the result from other studies, chromothripsis-like patterns in 2q, 3q, 10q, 12q, and 17p were not observed in this study.…”

Section: Discussionsupporting

confidence: 81%

Chromothripsis in Treatment Resistance in Multiple Myeloma

Lee

Yoon

et al. 2017

Genomics Inform

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Multiple myeloma (MM) is a malignant disease caused by an abnormal proliferation of plasma cells, of which the prognostic factors include chromosomal abnormality, β-2 microglobulin, and albumin. Recently, the term chromothripsis has emerged, which is the massive but highly localized chromosomal rearrangement in response to a one-step catastrophic event. Many studies have shown an association of chromothripsis with the prognosis in several cancers; however, few studies have investigated it in MM. Here, we studied the association between chromothripsis-like patterns and treatment resistance or prognosis. First, we analyzed nine MM cell lines (U266, MM.1S, RPMI8226, KMS-11, KMS-12-BM, KMS-12-PE, KMS-28-BM, KMS-28-PE, and NCI-H929) and bone marrow samples of four patients who were diagnosed with MM by next-generation sequencing-based copy number variation analysis. The frequency of the chromothripsis-like pattern was observed in seven cell lines. We analyzed the treatment-induced chromothripsis-like patterns in KMS-12-BM and KMS-12-PE cells. As a result, breakpoints and chromothripsis-like patterns were increased after drug treatment in the relatively resistant KMS-12-BM. We further analyzed the patients’ results according to the therapeutic response, which was divided into sensitive and resistant, as suggested by the International Myeloma Working Group. The chromothripsis-like pattern was more frequently observed in the resistant group. In the sensitive group, the frequency of the chromothripsis-like pattern decreased after treatment, whereas the resistant group showed increased chromothripsis-like patterns after the treatment. These results suggest that the chromothripsis-like pattern is associated with treatment response in MM.

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Section: Discussionsupporting

confidence: 81%

Chromothripsis in Treatment Resistance in Multiple Myeloma

Lee

Yoon

et al. 2017

Genomics Inform

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“…One of the major disadvantages of FISH method is the dependency to the quantity of bone marrow plasma cell percentage. Interphase FISH method with plasma cell enrichment by CD 138 labelling rather than examining on cultured bone marrow samples are suggested for higher detection rates of genetic abnormalities 8,9 . To date, European Myeloma Network recommends Interphase FISH method for MM and states as acceptable, till plasma cell enrichment methods becomes more accessable and less costly 10 .…”

Section: Discussionmentioning

confidence: 99%

Concepts of Double Hit and Triple Hit Disease in Multiple Myeloma, Entity and Prognostic Significance

Baysal

Demirci

Ümit

et al. 2020

Sci Rep

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Risk assessment in newly diagnosed multiple myeloma patients (NDMM) is the first and the most crucial determinant of treatment. With the utilization of fiSH analysis as a part of routine practice, high riskMultiple Myeloma (MM) is defined as having at least one of the mutations related with poor prognosis including; t(4;14) t(14;16), t(14;20), del 17p, p53 mutation, gain 1q and del 1p. M-Smart MM risk stratification guideline by Mayo Clinic has proposed a concept similar to high grade lymphomas. Having two of the high risk genetic abnormalities were defined as double hit MM and having any three as triple hit MM. Based on these definitions which may bring a much more clinically relatable understanding in MM prognosis, we aimed to assess our database regarding these two concepts and their probable significance in terms of outcome and prognosis. We retrospectively evaluated 159 newly diagnosed multiple myeloma patients and their clinical course. Among these patients; twenty-four patients have one high risk determinant and also seven and two patients were classified as double hit MM and triple hit MM respectively. Overall survival (OS) of the patients with double hit MM was 6 months, 32.0 months for patients with single high risk abnormality and 57.0 months for patients with no high risk abnormality. Univariate analysis showed that Double Hit and Triple Hit MM is a predictive of low OS. Hazard Ratio of patients with one high risk abnormality was 1.42, double-hit MM patients was 5.55, and triple-hit MM patients was 7.3. Despite the development of novel drugs and their effects of prolonging survival, the treatment has not been individualized. Understanding the biology of each patient as a unique process will be the success of the treatment. As it is known that some MM patients harbor high risk genetic abnormalities according to fiSH analysis, we can continue the argument that some patients bring an even higher risk and that can be defined as double or triple hit MM.

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“…Furthermore, the simultaneous measurement of signal intensity of each probe when compared to a normal reference together with the differentiation of alleles by genotype analysis of each SNP probe facilitates the determination of ploidy level. The clinical importance of this distinction has been demonstrated in MM patients where the use of genomic array platforms has prevented misinterpretation of a near‐tetraploid status, associated with an intermediate prognosis, with a hyperdiploid status, associated with a relatively good prognosis (Stevens‐Kroef et al, ).…”

Section: Clinical Utilitymentioning

confidence: 99%

Guidelines for genomic array analysis in acquired haematological neoplastic disorders

Schoumans

Suela²,

Hastings

et al. 2016

Genes Chromosomes & Cancer

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Genetic profiling is important for disease evaluation and prediction of prognosis or responsiveness to therapy in neoplasia. Microarray technologies, including array comparative genomic hybridization and single-nucleotide polymorphism-detecting arrays, have in recent years been introduced into the diagnostic setting for specific types of haematological malignancies and solid tumours. It can be used as a complementary test or depending on the neoplasia investigated, also as a standalone test. However, comprehensive and readable presentation of frequently identified complex genomic profiles remains challenging. To assist diagnostic laboratories, standardization and minimum criteria for clinical interpretation and reporting of acquired genomic abnormalities detected through arrays in neoplastic disorders are presented.

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High detection rate of clinically relevant genomic abnormalities in plasma cells enriched from patients with multiple myeloma

Cited by 22 publications

References 26 publications

Chromothripsis in Treatment Resistance in Multiple Myeloma

Chromothripsis in Treatment Resistance in Multiple Myeloma

Concepts of Double Hit and Triple Hit Disease in Multiple Myeloma, Entity and Prognostic Significance

Guidelines for genomic array analysis in acquired haematological neoplastic disorders

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