Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients
Por:
Medina, A, Jimenez, C, Sarasquete, ME, Gonzalez, M, Chillon, MC, Balanzategui, A, Prieto-Conde, I, Garcia-Alvarez, M, Puig, N, Gonzalez-Calle, V, Alcoceba, M, Cuenca, I, Barrio, S, Escalante, F, Gutierrez, NC, Gironella, M, Hernandez, MT, Sureda, A, Oriol, A, Blade, J, Lahuerta, JJ, San Miguel, JF, Mateos, MV, Martinez-Lopez, J, Calasanz, MJ and Garcia-Sanz, R
Publicada:
6 feb 2020
Ahead of Print:
6 feb 2020
Resumen:
Multiple myeloma is a heterogeneous disease whose pathogenesis has not been completely elucidated. Although B-cell receptors play a crucial role in myeloma pathogenesis, the impact of clonal immunoglobulin heavy-chain features in the outcome has not been extensively explored. Here we present the characterization of complete heavy-chain gene rearrangements in 413 myeloma patients treated in Spanish trials, including 113 patients characterized by next-generation sequencing. Compared to the normal B-cell repertoire, gene selection was biased in myeloma, with significant overrepresentation of IGHV3, IGHD2 and IGHD3, as well as IGHJ4 gene groups. Hypermutation was high in our patients (median: 8.8%). Interestingly, regarding patients who are not candidates for transplantation, a high hypermutation rate (>= 7%) and the use of IGHD2 and IGHD3 groups were associated with improved prognostic features and longer survival rates in the univariate analyses. Multivariate analysis revealed prolonged progression-free survival rates for patients using IGHD2/IGHD3 groups (HR: 0.552, 95% CI: 0.361-0.845, p = 0.006), as well as prolonged overall survival rates for patients with hypermutation >= 7% (HR: 0.291, 95% CI: 0.137-0.618, p = 0.001). Our results provide new insights into the molecular characterization of multiple myeloma, highlighting the need to evaluate some of these clonal rearrangement characteristics as new potential prognostic markers.
Filiaciones:
Medina, A:
IBMCC USAL CSIC, CIBERONC, Hosp Univ Salamanca HUSAL, IBSAL, Salamanca, Spain
Jimenez, C:
IBMCC USAL CSIC, CIBERONC, Hosp Univ Salamanca HUSAL, IBSAL, Salamanca, Spain
Sarasquete, ME:
IBMCC USAL CSIC, CIBERONC, Hosp Univ Salamanca HUSAL, IBSAL, Salamanca, Spain
Gonzalez, M:
IBMCC USAL CSIC, CIBERONC, Hosp Univ Salamanca HUSAL, IBSAL, Salamanca, Spain
Chillon, MC:
IBMCC USAL CSIC, CIBERONC, Hosp Univ Salamanca HUSAL, IBSAL, Salamanca, Spain
Balanzategui, A:
IBMCC USAL CSIC, CIBERONC, Hosp Univ Salamanca HUSAL, IBSAL, Salamanca, Spain
Prieto-Conde, I:
IBMCC USAL CSIC, CIBERONC, Hosp Univ Salamanca HUSAL, IBSAL, Salamanca, Spain
Garcia-Alvarez, M:
IBMCC USAL CSIC, CIBERONC, Hosp Univ Salamanca HUSAL, IBSAL, Salamanca, Spain
Puig, N:
IBMCC USAL CSIC, CIBERONC, Hosp Univ Salamanca HUSAL, IBSAL, Salamanca, Spain
Gonzalez-Calle, V:
IBMCC USAL CSIC, CIBERONC, Hosp Univ Salamanca HUSAL, IBSAL, Salamanca, Spain
Alcoceba, M:
IBMCC USAL CSIC, CIBERONC, Hosp Univ Salamanca HUSAL, IBSAL, Salamanca, Spain
Cuenca, I:
Hosp 12 Octubre, CIBERONC, Madrid, Spain
Barrio, S:
Hosp 12 Octubre, CIBERONC, Madrid, Spain
Escalante, F:
Complejo Hosp, Leon, Spain
Gutierrez, NC:
IBMCC USAL CSIC, CIBERONC, Hosp Univ Salamanca HUSAL, IBSAL, Salamanca, Spain
Gironella, M:
Hosp Valle De Hebron, Barcelona, Spain
Hernandez, MT:
Hosp Univ Canarias, San Cristobal la Laguna, Spain
Sureda, A:
Hosp Duran & Reynals, ICO, Barcelona, Spain
:
Hosp Badalona Germans Trias & Pujol, ICO, Inst Josep Carreras, Badalona, Spain
Blade, J:
Hosp Clin Barcelona, IDIBAPS, Barcelona, Spain
Lahuerta, JJ:
Hosp 12 Octubre, CIBERONC, Madrid, Spain
San Miguel, JF:
CUN, Ctr Invest Med Aplicada, CIBERONC, IDISNA, Pamplona, Spain
Mateos, MV:
IBMCC USAL CSIC, CIBERONC, Hosp Univ Salamanca HUSAL, IBSAL, Salamanca, Spain
Martinez-Lopez, J:
Hosp 12 Octubre, CIBERONC, Madrid, Spain
Calasanz, MJ:
CUN, Ctr Invest Med Aplicada, CIBERONC, IDISNA, Pamplona, Spain
Garcia-Sanz, R:
IBMCC USAL CSIC, CIBERONC, Hosp Univ Salamanca HUSAL, IBSAL, Salamanca, Spain
gold, Green Published
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