Clinical significance of cytogenetics and interphase fluorescence in situ hybridization analysis in newly diagnosed multiple myeloma in Taiwan

Introduction: Chromosomal abnormalities (CAs) have been identified as important factors in determining the biological features and prognostic value of multiple myeloma (MM). MYC gene-related abnormalities (MYC GAs) are one of the CAs, but its unfavorable impact has not been fully investigated in daily clinical practice. Methods: This study retrospectively analyzed the prognostic impact of MYC GAs on 81 patients through fluorescence in situ hybridization analysis in our institute. Results: MYC GAs were associated with poor overall survival (hazard ratio [HR], 3.08; 95% confidence interval [CI], 1.23–7.73; p = 0.017), progression-free survival (PFS) (HR, 2.96; 95% CI, 1.58–5.53; p < 0.001), and time to next treatment (TNT) (HR, 2.11; 95% CI, 1.13–3.93; p = 0.018) in the median follow-up of 34.7 months. Furthermore, MYC GAs with an additional chromosome 8 (MYC-Ch8(+)) were associated with shorter PFS (HR, 3.15; 95% CI, 1.38–7.2; p = 0.0064), whereas MYC GAs without an additional chromosome 8 (MYC-Ch8(−)) were associated with shorter PFS (HR, 3.62; 95% CI, 1.51–8.68; p = 0.004) and shorter TNT (HR, 3.72; 95% CI, 1.41–9.81; p = 0.0078). Conclusion: These findings could help identify high-risk patients with MM. Further prospective studies are needed to confirm the significance of MYC GAs for the MM prognostic effect.

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Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization

Blood ◽

10.1182/blood.v95.6.1925 ◽

2000 ◽

Vol 95 (6) ◽

pp. 1925-1930 ◽

Cited By ~ 220

Author(s):

Niklas Zojer ◽

Robert Königsberg ◽

Jutta Ackermann ◽

Elke Fritz ◽

Susanne Dallinger ◽

...

Keyword(s):

Multiple Myeloma ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Plasma Cells ◽

Clinical Importance ◽

Myeloma Cell ◽

Fish Analysis ◽

Newly Diagnosed ◽

Ki 67

Abstract Interphase fluorescence in situ hybridization (FISH) studies of chromosomal region 13q14 were performed to investigate the incidence and clinical importance of deletions in multiple myeloma (MM). Monoallelic deletions of the retinoblastoma-1 (rb-1) gene and the D13S319 locus were observed in 48 of 104 patients (46.2%) and in 28 of 72 (38.9%) patients, respectively, with newly diagnosed MM. FISH studies found that 13q14 was deleted in all 17 patients with karyotypic evidence of monosomy 13 or deletion of 13q but also in 9 of 19 patients with apparently normal karyotypes. Patients with a 13q14 deletion were more likely to have stage III disease (P = .022), higher serum levels of β2-microglobulin (P = .059), and a higher percentage of bone marrow plasma cells (P = .085) than patients with a normal 13q14 status on FISH analysis. In patients with a deletion of 13q14, myeloma cell proliferation (Ki-67) was markedly increased (22.0% ± 6.9% compared with 15.6% ± 8.2% in patients without the deletion;P = .0008). Evaluation of bromodeoxyuridine incorporation in 5 patients revealed that both rb-1–deleted and rb-1–normal MM subpopulations were proliferative. The presence of a 13q14 deletion on FISH analysis was associated with a significantly lower rate of response to conventional-dose chemotherapy (40.8% compared with 78.6%; P = .009) and a shorter overall survival (24.2 months compared with > 60 months; P < .005) than in patients without the deletion. Multivariate analysis of prognostic factors confirmed the independent predictive value of 13q14 deletions for shortened survival. In conclusion, deletions of 13q14 are frequently detected by interphase FISH in patients with newly diagnosed MM, correlate with increased proliferative activity, and represent an independent adverse prognostic feature in MM.

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