Concomitant gain of 1q21 and MYC translocation define a poor prognostic subgroup of hyperdiploid multiple myeloma

The detection of cytogenetic abnormalities in multiple myeloma (MM) has received more importance over last years for risk stratification and the new risk-adapted treatment strategies. Conventional G-banding analysis should be included in a routine procedure for the initial diagnostic workup for patients suspected of MM. However, the detection of chromosomal abnormalities in MM by conventional cytogenetics is limited owing to the low proliferative activity of malignant plasma cells as well as the low number of plasma cells in bone marrow specimens. Fluorescence in situ hybridization (FISH) or microarray-based technologies can overcome some of those drawbacks and detect specific target arrangements as well as chromosomal copy number changes. In this review, we will discuss different cytogenetic approaches and compare their strength and weakness to provide genetic information for risk stratification and prediction of outcome in MM patients.

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“…Translocations involving MYC are a secondary cytogenetic events and occur in 15%-20% of the patients with myeloma. 16,23,30 The…”

Section: Myc Translocationmentioning

confidence: 99%

“…MYC translocation is associated with a poor outcome and has a particularly negative impact in hyperdiploid subgroup. 16,30…”

Section: Myc Translocationmentioning

confidence: 99%

Recent advances in cytogenetic characterization of multiple myeloma

Saxe

Seo

Bergeron

et al. 2018

Int J Lab Hematology

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“…This confirms the hypothesis that MYC aberrations are secondary events and linked to progression from monoclonal gammopathy of undetermined significance to symptomatic MM as well as adverse outcome. 2,18 However, gains and deletions of MYC were only associated with adverse outcome if they were present as main clone. An explanation for this finding might be that main clonal gains of MYC were predominantly observed in patients with other high-risk CA in the main clone.…”

mentioning

confidence: 99%

Prognostic significance of cytogenetic heterogeneity in patients with newly diagnosed multiple myeloma

Merz¹,

Jauch

Hielscher

et al. 2017

Blood Advances

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“…While these data provide some explanations for the differential PFS benefit of IRd vs placebo‐Rd in TOURMALINE‐MM1, we recognize that our analyses have some limitations, including the small numbers of patients in each of the subgroups. Although we conducted a multivariate analysis incorporating various baseline disease characteristics, our analysis did not account for all the molecular subtypes, as these data were not collected in TOURMALINE‐MM1; for example, c‐MYC expression has been shown to be associated with hyperdiploidy . In addition, in the context of clonal evolution in MM, it would have been of value to incorporate data from bone marrow aspirates taken at diagnosis or earlier in the disease course; however, these data were not available.…”

Section: Discussionmentioning

confidence: 99%

c‐MYC expression and maturity phenotypes are associated with outcome benefit from addition of ixazomib to lenalidomide‐dexamethasone in myeloma

Bacco

Bahlis

Munshi

et al. 2020

European J of Haematology

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Objectives In the TOURMALINE‐MM1 phase 3 trial in relapsed/refractory multiple myeloma, ixazomib‐lenalidomide‐dexamethasone (IRd) showed different magnitudes of progression‐free survival (PFS) benefit vs placebo‐Rd according to number and type of prior therapies, with greater benefit seen in patients with >1 prior line of therapy or 1 prior line of therapy without stem cell transplantation (SCT). Methods RNA sequencing data were used to investigate the basis of these differences. Results The PFS benefit of IRd vs placebo‐Rd was greater in patients with tumors expressing high c‐MYC levels (median not reached vs 11.3 months; hazard ratio [HR] 0.42; 95% CI, 0.26, 0.66; P < .001) compared with in those expressing low c‐MYC levels (median 20.6 vs 16.6 months; HR 0.75; 95% CI, 0.42, 1.2). Expression of c‐MYC in tumors varied based on the number and type of prior therapy received, with the lowest levels observed in tumors of patients who had received 1 prior line of therapy including SCT. These tumors also had higher expression levels of CD19 and CD81. Conclusions PFS analyses suggest that lenalidomide and ixazomib target tumors with different levels of c‐MYC, CD19, and CD81 expression, thus providing a potential rationale for the differential benefits observed in the TOURMALINE‐MM1 study. This trial was registered at http://www.clinicaltrials.gov as: NCT01564537

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Concomitant gain of 1q21 and MYC translocation define a poor prognostic subgroup of hyperdiploid multiple myeloma

Cited by 38 publications

References 9 publications

Recent advances in cytogenetic characterization of multiple myeloma

Recent advances in cytogenetic characterization of multiple myeloma

Prognostic significance of cytogenetic heterogeneity in patients with newly diagnosed multiple myeloma

c‐MYC expression and maturity phenotypes are associated with outcome benefit from addition of ixazomib to lenalidomide‐dexamethasone in myeloma

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