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Interphase Fluorescence in situ Hybridization of Bone Marrow Smears of Multiple Myeloma
Published on: April 15, 2022
Evaluation of bone disease in multiple myeloma patients carrying the t(4;14) chromosomal translocation
Patrizia Tosi1, Carolina Terragna, Nicoletta Testoni
1Seràgnoli Institute of Hematology and Medical Oncology, Bologna University, Bologna, Italy. ptosi@med.unibo.it
Abstract:
T(4;14) chromosomal abnormality is one of the most adverse prognostic factors predicting for poor outcome in multiple myeloma (MM) patients. It has been recently suggested that bone disease, as evaluated by spinal magnetic resonance imaging (MRI), is relatively infrequent in these patients. 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 with negative patients. For this purpose, 53 consecutive newly diagnosed MM patients (35M, 18F, median age = 55 yr) underwent evaluation of total skeletal X-ray, whole spine MRI, and at the same time, quantification of markers of bone resorption (urinary N-terminal telopeptide, pyridinoline, deoxypyridinoline, serum crosslaps), and bone formation (bone alkaline phosphatase and osteocalcin) was performed. The presence of IgH/MMSET fusion gene as a surrogate marker for t(4;14), was detected in 11 patients (20.7%), whose clinical characteristics were similar to those observed in t(4;14) negative patients. The type of marrow involvement at spinal MRI (diffuse vs. focal vs. negative) was the same in both groups of patients, even though overt vertebral fractures were more frequently found in t(4;14) positive cases (82% vs. 43%, P = 0.05); in line with this finding, skeletal lesions were more common in t(4;14) positive patients (mean skeletal score = 8.54 +/- 1.36 SE, as compared with 3.42 +/- 0.57 SE in t(4;14) negative cases, P = 0.000). These data were confirmed by the evaluation of serum crosslaps, that were significantly increased in patients with t(4;14) abnormality as compared with negative individuals (10,400 pmol/L +/- 2160 SE vs. 5640 pmol/L +/- 859 SE P = 0.02) Our results indicate that, at variance to what has been previously reported, bone resorption is more prominent in t(4;14) positive patients.
Insights
The T(4;14) chromosomal abnormality in multiple myeloma patients is linked to increased bone resorption and skeletal lesions, contrary to previous findings. This adverse prognostic factor impacts bone health more significantly than previously understood.
Area of Science:
- Hematology
- Oncology
- Skeletal Biology
Background:
- The T(4;14) chromosomal abnormality is a known adverse prognostic factor in multiple myeloma (MM).
- Previous research suggested bone disease is infrequent in MM patients with T(4;14).
Purpose of the Study:
- To investigate the extent of bone involvement in MM patients with T(4;14) compared to those without.
- To analyze bone resorption and formation markers in relation to the T(4;14) translocation.
Main Methods:
- Evaluated 53 newly diagnosed MM patients using skeletal X-rays and spinal MRI.
- Quantified bone resorption markers (urinary N-telopeptide, serum crosslaps) and bone formation markers (bone alkaline phosphatase, osteocalcin).
- Detected T(4;14) via IgH/MMSET fusion gene analysis.
Main Results:
- T(4;14) was detected in 20.7% of patients; clinical characteristics were similar to negative patients.
- T(4;14) positive patients showed more frequent vertebral fractures (82% vs. 43%).
- Significantly higher skeletal lesion scores (8.54 vs. 3.42) and increased serum crosslaps (10,400 vs. 5640 pmol/L) in T(4;14) positive patients.
Conclusions:
- Contrary to prior reports, bone resorption is more prominent in MM patients with the T(4;14) abnormality.
- The T(4;14) translocation is associated with more extensive bone disease and fractures.
- These findings highlight the importance of assessing bone health in T(4;14) positive MM patients.
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