Abstract

Chromosomal translocations involving the immunoglobulin heavy chain switch region (IgH) are quite common in multiple myeloma (MM), and some of them can reliably predict disease outcome. In particular, t(4;14) chromosomal abnormality is one of the most adverse prognostic factors for response duration and survival after high dose therapy and autologous stem cell transplantation. Despite the dismal prognosis, however, in this subset of patients, bone involvement, as evaluated by spine MRI, is relatively infrequent, at variance to what has been observed in other MM subtypes according to TC classification. In the present study we aimed at further testing this hypothesis by analyzing the extent of whole bone involvement in patients showing t(4;14) chromosomal translocation as compared to negative patients. For this purpose, 50 newly diagnosed MM patients (32M, 18F, median age = 54 yrs) underwent evaluation of total skeletal X-ray, whole spine MRI and, at the same time, quantification of markers of bone resorption (urinary NTX, PYR and DPYR and serum crosslaps) and bone formation (bone alkaline phosphatase-BAP and osteocalcin) was performed. Using a real-time PCR assay to detect the presence of IgH/MMSET fusion gene as a surrogate marker for t(4;14), we found 15 patients carrying this chromosomal abnormality, 7 of whom (46%) were also positive for the deletion of chromosome 13, this abnormality was detected in 11/35 (31%) patients who proved negative for IgH/MMSET hybrid transcript. The two groups of patients did not differ significantly in terms of median age, distribution of M protein isotype and light chain, beta-2 microglobulin, bone marrow plasma cell infiltration and disease stage. Spinal MRI was negative in 3/15 (20%) t(4;14) positive patients as compared to 12% t(4;14) negative patients; skeletal involvement, however, was more pronounced in t(4;14) positive patients (median skeletal score = 6.24, as compared to 3.58 in t(4;14) negative cases, p= 0.00). These data were confirmed by the evaluation of bone resorption markers; specifically, serum crosslaps were significantly increased in patients with t(4;14) abnormality compared to negative individuals (7984 pmol/L±1682SE vs 5123pmol/L±783SE p=0.04). Conversely, no difference in bone formation markers was found in the two groups of patients. Our results indicate that, despite a spinal involvement at MRI that is comparable to what is observed in negative patients, individuals who are t(4;14) positive show a more pronounced bone resorption pattern, this in contrast to what has been reported so far, but in line with the aggressive features of the disease in these patients.

Disclosure: No relevant conflicts of interest to declare.

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