Contributions
Abstract: PB2167
Type: Publication Only
Background
MYC rearrangements (MYCr) are late progression events in multiple myeloma (MM). Reported frequency differs considerably among studies ranging from 15% and up to 50% of MM patients. Increased c-MYC expression was found to be involved in MM progression, is associated with it’s aggressive nature, short remissions and overall survival.
Aims
We determined the frequency and type of MYCr in newly diagnosed MM patients in Slovenija and analysed correlation with concomitant cytogenetic aberrations as well as with some clinical parameters.
Methods
69 patients were included, aged 45 to 93 (median 68) years. Observation time was 0-8.3 years with (median 1.1 year). MYC was analysed in all but one patient before the induction MM treatment. MYC rearrangement was determined on CD-138 isolated plasma cells by FISH which was also used to detect other MM specific cytogenetic abnormalities: del(13q), del(17p), IGH rearrangements, amp(1q), del(1p), and hyperdiploidy. Poseidon DNA probe MYC TC with established cut-off value 2.5% was used not only to detect MYCr but trough the co-localization patterns of signals also to distinguish different breakpoints in MYC gene. Differences between categorical variables were determined by Fisher’s exact test using Medcalc software.
Results
MYCr was found in 17% (12/69) of patients. The clone size ranged from 5 - 99% of plasma cells. We observed all three breakpoints: distal and proximal to MYC gene and in the MYC gene. Dominant breakage variant in 7/12 pts was distal. The later was commonly observed as a sole subtype as well as a prevailing clone. Besides typical signals also proximal and distal breakage accompanied by deletion of the corresponding chromosomal region was observed. Considering other routinely determined chromosomal rearrangements, MYC was more frequently rearranged in patients with del(13q) (P=0.004), amp(1q) (P=0.035), and hyperdiploidy (P=0.012). MYCr was found in 2/12 patients as a sole abnormality. MYCr was accompanied with secondary cytogenetic changes In 9/10 patients and only in 1/10 patients with primary change (hyperdiploidy). The difference between groups was significant (P=0.0011). When we focused on cytogenetic risk groups 25% (7/28) of patients in high risk group was MYC positive, while only 19% (4/21) and 6% (1/17) of patients were positive in standard and low risk group respectively. Difference among groups was however, not statistically significant. For 52 patients clinical data were available. We couldn’t find difference between MYC positive and negative groups for ISS score and due to the short observation time neither for non-responsiveness to induction MM treatment and survival.
Conclusion
The observed frequency of MYCr in our cohort of almost exclusively newly diagnosed MM patients is consistent with previous literature reports. We observed strong correlation between MYCr and secondary chromosomal aberrations as well as with overall high risk cytogenetic group. This confirms not only that MYCr itself is a secondary genetic event but also the need for its early recognition and more effective/specific therapeutic approaches in MYCr patients. The short observation time is a limitation of the current analysis but will enable us to obtain valuable data in the future work. Namely, majority of MM patients were treated with the same therapeutic regimen.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Cytogenetic abnormalities, High risk, Multiple Myeloma, MYC
Abstract: PB2167
Type: Publication Only
Background
MYC rearrangements (MYCr) are late progression events in multiple myeloma (MM). Reported frequency differs considerably among studies ranging from 15% and up to 50% of MM patients. Increased c-MYC expression was found to be involved in MM progression, is associated with it’s aggressive nature, short remissions and overall survival.
Aims
We determined the frequency and type of MYCr in newly diagnosed MM patients in Slovenija and analysed correlation with concomitant cytogenetic aberrations as well as with some clinical parameters.
Methods
69 patients were included, aged 45 to 93 (median 68) years. Observation time was 0-8.3 years with (median 1.1 year). MYC was analysed in all but one patient before the induction MM treatment. MYC rearrangement was determined on CD-138 isolated plasma cells by FISH which was also used to detect other MM specific cytogenetic abnormalities: del(13q), del(17p), IGH rearrangements, amp(1q), del(1p), and hyperdiploidy. Poseidon DNA probe MYC TC with established cut-off value 2.5% was used not only to detect MYCr but trough the co-localization patterns of signals also to distinguish different breakpoints in MYC gene. Differences between categorical variables were determined by Fisher’s exact test using Medcalc software.
Results
MYCr was found in 17% (12/69) of patients. The clone size ranged from 5 - 99% of plasma cells. We observed all three breakpoints: distal and proximal to MYC gene and in the MYC gene. Dominant breakage variant in 7/12 pts was distal. The later was commonly observed as a sole subtype as well as a prevailing clone. Besides typical signals also proximal and distal breakage accompanied by deletion of the corresponding chromosomal region was observed. Considering other routinely determined chromosomal rearrangements, MYC was more frequently rearranged in patients with del(13q) (P=0.004), amp(1q) (P=0.035), and hyperdiploidy (P=0.012). MYCr was found in 2/12 patients as a sole abnormality. MYCr was accompanied with secondary cytogenetic changes In 9/10 patients and only in 1/10 patients with primary change (hyperdiploidy). The difference between groups was significant (P=0.0011). When we focused on cytogenetic risk groups 25% (7/28) of patients in high risk group was MYC positive, while only 19% (4/21) and 6% (1/17) of patients were positive in standard and low risk group respectively. Difference among groups was however, not statistically significant. For 52 patients clinical data were available. We couldn’t find difference between MYC positive and negative groups for ISS score and due to the short observation time neither for non-responsiveness to induction MM treatment and survival.
Conclusion
The observed frequency of MYCr in our cohort of almost exclusively newly diagnosed MM patients is consistent with previous literature reports. We observed strong correlation between MYCr and secondary chromosomal aberrations as well as with overall high risk cytogenetic group. This confirms not only that MYCr itself is a secondary genetic event but also the need for its early recognition and more effective/specific therapeutic approaches in MYCr patients. The short observation time is a limitation of the current analysis but will enable us to obtain valuable data in the future work. Namely, majority of MM patients were treated with the same therapeutic regimen.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Cytogenetic abnormalities, High risk, Multiple Myeloma, MYC