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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.

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Related in: MedlinePlus

Survival analysis in newly diagnosed MM patients(A) Patients with del(12p13) had obviously inferior PFS (P < 0.001) when compared to patients without del(12p13). (B) Patients with del(12p13) had obviously inferior OS (P < 0.001) when compared to patients without del(12p13).
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Figure 2: Survival analysis in newly diagnosed MM patients(A) Patients with del(12p13) had obviously inferior PFS (P < 0.001) when compared to patients without del(12p13). (B) Patients with del(12p13) had obviously inferior OS (P < 0.001) when compared to patients without del(12p13).

Mentions: Follow-up data from 241 patients were analyzed to ascertain the prognostic value of 12p13 deletion in newly diagnosed MM patients. Totally 34 patients did not complete the follow-up examination due to poor contact information. The results showed that patients with del(12p) had significantly shortened PFS (11.0 vs. 24.0 months, P < 0.001) and OS (17.0 vs. 40.0 months, P < 0.001) than the patients without del(12p) (Figure 2A and 2B). In addition, we also investigated the impact of 12p13 gain on survival; however, no prognosis significance of 12p13 gain was observed in the present study. We further analyzed other risk factors that might affect the prognosis of this series of patients. Based on the univariate analysis shown in Table 3, patients with ISS stage III, LDH higher than 220 U/L, del(13q), del(17p), t(4;14), amp(1q21) and high-risk genetic abnormality had inferior survival than the control group. In multivariate analysis, when adjusted to the above prognostic variables, del(12p13) remained the powerful independent adverse factor for PFS (HR 2.29, 95% CI: 1.25–4.18, P = 0.007) and OS (HR 2.11, 95% CI: 1.07–4.17, P = 0.032). The other two independent factors were del(17p) (PFS: HR 2.50, 95% CI: 1.42–4.38, P = 0.001; OS: HR 1.90, 95% CI: 0.99–3.68, P = 0.050) and amp(1q21) (PFS: HR 2.67, 95% CI: 1.68–4.24, P < 0.001; OS: HR 1.91, 95% CI: 1.13–3.24, P = 0.016) (Table 4).


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)

Survival analysis in newly diagnosed MM patients(A) Patients with del(12p13) had obviously inferior PFS (P < 0.001) when compared to patients without del(12p13). (B) Patients with del(12p13) had obviously inferior OS (P < 0.001) when compared to patients without del(12p13).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Survival analysis in newly diagnosed MM patients(A) Patients with del(12p13) had obviously inferior PFS (P < 0.001) when compared to patients without del(12p13). (B) Patients with del(12p13) had obviously inferior OS (P < 0.001) when compared to patients without del(12p13).
Mentions: Follow-up data from 241 patients were analyzed to ascertain the prognostic value of 12p13 deletion in newly diagnosed MM patients. Totally 34 patients did not complete the follow-up examination due to poor contact information. The results showed that patients with del(12p) had significantly shortened PFS (11.0 vs. 24.0 months, P < 0.001) and OS (17.0 vs. 40.0 months, P < 0.001) than the patients without del(12p) (Figure 2A and 2B). In addition, we also investigated the impact of 12p13 gain on survival; however, no prognosis significance of 12p13 gain was observed in the present study. We further analyzed other risk factors that might affect the prognosis of this series of patients. Based on the univariate analysis shown in Table 3, patients with ISS stage III, LDH higher than 220 U/L, del(13q), del(17p), t(4;14), amp(1q21) and high-risk genetic abnormality had inferior survival than the control group. In multivariate analysis, when adjusted to the above prognostic variables, del(12p13) remained the powerful independent adverse factor for PFS (HR 2.29, 95% CI: 1.25–4.18, P = 0.007) and OS (HR 2.11, 95% CI: 1.07–4.17, P = 0.032). The other two independent factors were del(17p) (PFS: HR 2.50, 95% CI: 1.42–4.38, P = 0.001; OS: HR 1.90, 95% CI: 0.99–3.68, P = 0.050) and amp(1q21) (PFS: HR 2.67, 95% CI: 1.68–4.24, P < 0.001; OS: HR 1.91, 95% CI: 1.13–3.24, P = 0.016) (Table 4).

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