The impact of C-Myc gene-related aberrations in newly diagnosed myeloma with bortezomib/dexamethasone therapy

Abstract

Recent studies have suggested that c-Myc over-expression may be a factor indicating poor prognosis in multiple myeloma (MM), although c-Myc gene-related abnormalities, including translocation and gene amplification, have not been fully investigated in the novel agent era. Additional chromosome 8 may be considered as aggressive disease in the 1990s. To clarify the impact of these aberrations, we retrospectively analyzed newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM) with bortezomib and dexamethasone induction therapy. In the present study, the high-risk group was defined as having at least one of the following present: non-hyperdiploidy, IgH/FGFR3, and del p53. Forty NDMM cases were analyzed. At the median follow-up duration of 14.1 months, 14 RRMM were recognized. The proportions of patients in the high-risk, c-Myc gene-related aberrations, and additional chromosome 8 groups at diagnosis were 45.5, 22.5, and 10 %, respectively. The proportions of patients who developed RRMM in the high-risk, c-Myc gene-related aberrations, and additional chromosome 8 groups were 41.7, 77.7, and 50 %, respectively. Furthermore, patients with c-Myc gene-related abnormalities tended to exhibit inferior progression-free survival (PFS), and those with c-Myc gene-related abnormalities and/or additional chromosome 8 showed statistically shorter PFS. Therefore, c-Myc gene-related abnormalities and additional chromosome 8 may be related to a poorer prognosis.

Proteasomal Inhibition by Ixazomib Induces CHK1 and MYC-Dependent Cell Death in T-cell and Hodgkin Lymphoma

“…Studies in transgenic mouse models showed that even brief MYC inactivation is sufficient to induce tumor regressions (48) and that targeting MYC may destabilize apoptosis regulatory network and induce cell death in lymphoma (49). In multiple myeloma, a correlation between MYC overexpression (50) and poor response to treatment with bortezomib has been reported, and in mantle cell lymphoma, co-targeting MYC with (CPI203) was shown to overcome bortezomib resistance (51). While these studies show a correlation between MYC and resistance to proteasome inhibition, results from our experiments demonstrated the biological mechanism for MYC dependent resistance to proteasome inhibition, and moreover, how to circumvent these mechanisms to improve therapeutic response.…”

A concise revised Myeloma Comorbidity Index as a valid prognostic instrument in a large cohort of 801 multiple myeloma patients

“…27 Unfavorable cytogenetics were defined as del(17p13), del(13q14), t(4;14), t(14;16), t(14;20), hypodiploidy, c-myc and chromosome 1 aberrations. 1,8,10,22,24,27–31 The KPS was defined as normal (100%), mildly (90%), moderately (80%) or more substantially impaired (≤70%). Frailty and disability were assessed in order to get a more precise determination of patients’ physical condition.…”

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

“…1,2 Desiree Kirn, 3 Anja Seckinger, 1 Thomas Hielscher, 4 Martin Granzow, 3 Uta Bertsch, 1 Gerlinde Egerer, 1 Hans Salwender, 5 Igor W. Blau,…”