Interphase Fluorescence In situ Hybridization Analysis Of 14q32 Rearrangements [t(4;14) and t(11;14)] In Egyptian Patients With Plasma Cell Myeloma

Abstract

SUMMARY AND CONCLUSION P lasma cell myeloma is a clonal bone marrow disease characterized by the neoplastic transformation of differentiated B cells with the accumulation of malignant plasma cells in the bone marrow compartment. Clinically, patients are characterized by excess bone marrow plasma cells, serum and or urine monoclonal protein, osteolytic bony lesions, anemia, hypercalcemia and renal impairment. This disease is considered heterogenous both at the genetic level and in terms of clinical outcome. Plasma cell myeloma accounts for approximately 1-2 % of all malignant diseases, 10-15 % of all hematological malignancies and causes 20% of deaths from hematologic malignancies. Chromosomal aberrations in MM are typically complex and represent a hallmark of the disease, involving many chromosomes that are altered both numerically and structurally. The most frequent structural aberrations are 14q32 IgH rearrangement with t(11;14) (q13;q32) being the most frequently detected 14q32 translocation. The low proliferative activity of the tumor cells early in the disease is an important limitation of conventional cytogenetics (karyotyping) since only dividing cells can be analyzed. Yet, this limitation has been overcomed by the use of molecular cytogenetic techniques as FISH, Gene expression profiling (GEP) and single nucleotide polymorphism (SNP) arrays. Nowadays, the standard diagnostic work up for myeloma includes both iFISH and traditional metaphase chromosomal studies. The present study was done on 31 newly diagnosed Egyptian myeloma patients recruited from inpatient and outpatient clinics of Clinical Hematology and Oncology department, Ain Shams University Hospitals and aimed to detect the incidence 14q32 IgH rearrangement, t(11;14) and t(4;14) by iFISH and their relation to the standard prognostic factors and patients’ outcome . All the patients were subjected to complete history, clinical and laboratory examination. Moreover, we have also tested the expression of 14q32 IgH rearrangement by using the LSI IGH dual color FISH break apart rearrangement probe (14q32), we also used the LSI IGH/CCND1 DF Probe for detection of t(11;14)(q13;q32), LSI IGH/FGFR3 DF Probe for detection of t(4;14)(p16;q32), LSI D13S319 (13q14.3) probe for detection of 13q del and LSI TP53 Probe for detection of 17p del on bone marrow samples collected from the patients at diagnosis. In the present study, there were statistical significant decrease in mean total leucocytic count and mean serum albumin level in patients showing positive genetic abnormalities detected by iFISH whereas a significant increase in β2-microglobulin level (>5.5mg/dL) and kappa light chain are detected in the same group. Morever, stage III are significantly demonstrated as well as poor outcome in patients showing positive iFISH abnormalities. There were statistical significant decrease in both serum calcium (<10 mg/dl) and serum LDH levels (<300 IU/L) found in the patients with positive t(11;14). t(11;14) is prognostically associated with a better outcome. There were statistical significant decrease found in patients with positive t(4;14) in the present study as regards to mean of each of calcium, LDH and BUN serum levels. t(4;14) was significantly manifested in patients with low platelet count (<150x109/L) and in patients aged over 60 years. A strong association has been detected between positive 17p13 del and high mean value of β2-microglobulin serum level. There was a significant decrease in total leucocytic count in 17p13 del positive cases. As regards to the prognostic impact of 13q del, this chromosomal aberration is associated with a poor outcome. There was also significant decrease in mean albumin level in patients with positive 13q del.