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Heterogeneous chromosome 12p deletion is an independent adverse prognostic factor and resistant to bortezomib-based therapy in multiple myeloma.

Li F, Xu Y, Deng P, Yang Y, Sui W, Jin F, Hao M, Li Z, Zang M, Zhou D, Gu Z, Ru K, Wang J, Cheng T, Qiu L - Oncotarget (2015)

Bottom Line: Patients with del(12p) conferred significantly adverse prognosis for PFS and OS, even in patients subjected to bortezomib-based therapy.In addition, del(12p13) combined with high β2-MG, high LDH and bone lesion can further identify subpopulations with high-risk features.Our results strongly supported that del(12p13) can be used as a valuable prognostic marker in MM.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.

ABSTRACT
The deletion of 12p (del(12p)) has been described as a novel negative prognostic marker in multiple myeloma (MM) and has gained increasing attention in recent years. However, its impact on MM is still controversial. In this study, we comprehensively evaluated the clinical impact of 12p13 deletion using fluorescence in situ hybridization (FISH) on 275 newly diagnosed MM cases treated in a prospective, non-randomized clinical trial (BDH 2008/02). The results showed that deletion of 12p13 was detected in 10.5% of newly diagnosed cases and associated with multiple indicators for high tumor burden including ISS III, BM plasmacytosis larger than 50%, and renal lesion. Moreover, the cases with 12p13 deletion typically had higher incidence of del(17p), IGH translocation and t(4;14). Patients with del(12p) conferred significantly adverse prognosis for PFS and OS, even in patients subjected to bortezomib-based therapy. When adjusted to the established prognostic variables including del(13q), del(17p), t(4;14), amp(1q21), ISS stage and LDH, del(12p13) remained the powerful independent adverse factor for PFS (P = 0.007) and OS (P = 0.032). In addition, del(12p13) combined with high β2-MG, high LDH and bone lesion can further identify subpopulations with high-risk features. Our results strongly supported that del(12p13) can be used as a valuable prognostic marker in MM.

No MeSH data available.


Related in: MedlinePlus

The deletion (A) and amplification (B) rates in plasma cell dyscrasias
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Figure 1: The deletion (A) and amplification (B) rates in plasma cell dyscrasias

Mentions: In this series of 380 patients, the deletion of 12p13 was detected in 29 (10.5%) of 275 newly diagnosed and 13 (14.4%) of 90 relapsed patients (P = 0.314). Moreover, in patients with sPCL, 37.5% (3/8) of patients with 12p13 deletion were detected and revealed higher deletion rate than newly diagnosed and relapsed patients (P = 0.008, 0.051). However, none of 7 MGUS patients had this deletion. Interestingly, we also found that 4.4% (12/275) of newly diagnosed and 12.2% (11/90) of relapsed patients had 12p13 gain and revealed the higher gain rate in relapsed patients (P = 0.008). The comparison of deletion/gain rate in patients with plasma cell dyscrasias was shown in Figure 1A and 1B.


Heterogeneous chromosome 12p deletion is an independent adverse prognostic factor and resistant to bortezomib-based therapy in multiple myeloma.

Li F, Xu Y, Deng P, Yang Y, Sui W, Jin F, Hao M, Li Z, Zang M, Zhou D, Gu Z, Ru K, Wang J, Cheng T, Qiu L - Oncotarget (2015)

The deletion (A) and amplification (B) rates in plasma cell dyscrasias
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496228&req=5

Figure 1: The deletion (A) and amplification (B) rates in plasma cell dyscrasias
Mentions: In this series of 380 patients, the deletion of 12p13 was detected in 29 (10.5%) of 275 newly diagnosed and 13 (14.4%) of 90 relapsed patients (P = 0.314). Moreover, in patients with sPCL, 37.5% (3/8) of patients with 12p13 deletion were detected and revealed higher deletion rate than newly diagnosed and relapsed patients (P = 0.008, 0.051). However, none of 7 MGUS patients had this deletion. Interestingly, we also found that 4.4% (12/275) of newly diagnosed and 12.2% (11/90) of relapsed patients had 12p13 gain and revealed the higher gain rate in relapsed patients (P = 0.008). The comparison of deletion/gain rate in patients with plasma cell dyscrasias was shown in Figure 1A and 1B.

Bottom Line: Patients with del(12p) conferred significantly adverse prognosis for PFS and OS, even in patients subjected to bortezomib-based therapy.In addition, del(12p13) combined with high β2-MG, high LDH and bone lesion can further identify subpopulations with high-risk features.Our results strongly supported that del(12p13) can be used as a valuable prognostic marker in MM.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.

ABSTRACT
The deletion of 12p (del(12p)) has been described as a novel negative prognostic marker in multiple myeloma (MM) and has gained increasing attention in recent years. However, its impact on MM is still controversial. In this study, we comprehensively evaluated the clinical impact of 12p13 deletion using fluorescence in situ hybridization (FISH) on 275 newly diagnosed MM cases treated in a prospective, non-randomized clinical trial (BDH 2008/02). The results showed that deletion of 12p13 was detected in 10.5% of newly diagnosed cases and associated with multiple indicators for high tumor burden including ISS III, BM plasmacytosis larger than 50%, and renal lesion. Moreover, the cases with 12p13 deletion typically had higher incidence of del(17p), IGH translocation and t(4;14). Patients with del(12p) conferred significantly adverse prognosis for PFS and OS, even in patients subjected to bortezomib-based therapy. When adjusted to the established prognostic variables including del(13q), del(17p), t(4;14), amp(1q21), ISS stage and LDH, del(12p13) remained the powerful independent adverse factor for PFS (P = 0.007) and OS (P = 0.032). In addition, del(12p13) combined with high β2-MG, high LDH and bone lesion can further identify subpopulations with high-risk features. Our results strongly supported that del(12p13) can be used as a valuable prognostic marker in MM.

No MeSH data available.


Related in: MedlinePlus