Prognostic value of 13q14 deletion and IgH 14q32 rearrangement by interphase fluorescence in situ hybridization in patients with multiple myeloma

Abstract

Background: Multiple myeloma (MM) is a clonal bone marrow (BM) disease characterized by the neoplastic transformation of differentiated B cells with the accumulation of malignant plasma cells in the BM compartment. In Egypt, its extrapolated prevalence is 17,630/76,117,421 with annual rate around 4,085/76,117,421. Chromosomal aberrations in MM are typically complex and represent a hallmark of the disease. The most frequent structural aberrations are 13q14 deletion detected in 33-50% of the cases and 14q32 IgH rearrangement detected in 60-70% of the cases with t (11;14) (q13;q32) being the most frequently detected 14q32 translocation seen in 15% of these patients. Aim: The aim was to detect both 13q14 deletion and 14q32 IgH rearrangement by interphase fluorescence in situ hybridization (I-FISH) on 100 newly diagnosed Egyptian myeloma patients and their relation to the patients′ outcome and prognosis. Subjects and Methods: Patients were subjected to a complete history, clinical examination, and laboratory. We have also tested the expression of 13q14 deletion by locus-specific identifier (LSI) D13S319 probe assay and 14q32 IgH rearrangement by IgH dual color FISH break-apart assay on BM aspirates collected from the patients at diagnosis (before starting therapy). Staging and follow-up of the patients were carried out to detect the outcome of the disease. Results: We found that 65% of the examined myeloma patients showed genetic aberrations (13q14 deletion, 14q32 IgH rearrangement or both) by I-FISH. Of which, 40% were positive only for 13q14 deletion, 20% were positive only for 14q32 IgH rearrangement and only 5% were positive for both aberrations. 13q14 deletion was associated with more patients being resistant to chemotherapy or dying indicating its poor impact on patients′ prognosis, whereas 14q32 IgH rearrangement was associated with more patients in remission indicating its good impact on patients′ prognosis. Comparing myeloma patients who went into remission to those who died or were resistant to chemotherapy after receiving treatment, revealed highly statistical significance in these patients (P ≤ 0.001) as regards to their serum calcium, albumin, B2 microglobulin, and BM clonal plasma cell levels with P values (0.0009, 0.0001, 0.0001 and 0.0001, respectively). Moreover, a statistical significance (P ≤ 0.05) was found in these patients as regards to their total protein and serum M-component with P values (0.0288 and 0.0182, respectively). Summary/Conclusion: 13q14 deletion detected by LSI D13S319 FISH probe in myeloma patients was seen in 40% of the studied cases and was associated with patients being resistant to chemotherapy or dying. Whereas, 14q32 IgH rearrangement detected by IgH dual color break-apart FISH assay in these patients was seen in 20% of the studied cases and was associated with patients in remission.

Keywords

• 13q14 deletion
• multiple myeloma
• Igh 14q32 rearrangement