TY - JOUR
T1 - A gene signature that distinguishes conventional and leukemic nonnodal mantle cell lymphoma helps predict outcome
AU - Clot, Guillem
AU - Jares, Pedro
AU - Giné, Eva
AU - Navarro, Alba
AU - Royo, Cristina
AU - Pinyol, Magda
AU - Martín-Garcia, David
AU - Demajo, Santiago
AU - Espinet, Blanca
AU - Salar, Antonio
AU - Ferrer, Ana
AU - Muntañola, Ana
AU - Aymerich, Marta
AU - Rauert-Wunderlich, Hilka
AU - Jaffe, Elaine S.
AU - Connors, Joseph M.
AU - Gascoyne, Randy D.
AU - Delabie, Jan
AU - López-Guillermo, Armando
AU - Ott, German
AU - Wright, George W.
AU - Staudt, Louis M.
AU - Rosenwald, Andreas
AU - Scott, David W.
AU - Rimsza, Lisa M.
AU - Beà, Sílvia
AU - Campo, Elías
N1 - Publisher Copyright:
Copyright 2011 by The American Society of Hematology; all rights reserved.
PY - 2018/7/26
Y1 - 2018/7/26
N2 - Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy, but some patients have a very indolent evolution. This heterogeneous course is related, in part, to the different biological characteristics of conventional MCL (cMCL) and the distinct subgroup of leukemic nonnodal MCL (nnMCL). Robust criteria to distinguish these MCL subtypes and additional biological parameters that influence their evolution are not well defined. We describe a novel molecular assay that reliably distinguishes cMCL and nnMCL using blood samples. We trained a 16-gene assay (L-MCL16 assay) on the NanoString platform using 19 purified leukemic samples. The locked assay was applied to an independent cohort of 70 MCL patients with leukemic presentation. The assay assigned 37% of cases to nnMCL and 56% to cMCL. nnMCL and cMCL differed in nodal presentation, lactate dehydrogenase, immunoglobulin heavy chain gene mutational status, management options, genomic complexity, and CDKN2A/ATM deletions, but the proportion with 17p/TP53 aberrations was similar in both subgroups. Sequential samples showed that assay prediction was stable over time. nnMCL had a better overall survival (OS) than cMCL (3-year OS 92% vs 69%; P 5 .006) from the time of diagnosis and longer time to first treatment. Genomic complexity and TP53/CDKN2A aberrations predicted for shorter OS in the entire series and cMCL, whereas only genomic complexity was associated with shorter time to first treatment and OS in nnMCL. In conclusion, the newly developed assay robustly recognizes the 2 molecular subtypes of MCL in leukemic samples. Its combination with genetic alterations improves the prognostic evaluation and may provide useful biological information for management decisions.
AB - Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy, but some patients have a very indolent evolution. This heterogeneous course is related, in part, to the different biological characteristics of conventional MCL (cMCL) and the distinct subgroup of leukemic nonnodal MCL (nnMCL). Robust criteria to distinguish these MCL subtypes and additional biological parameters that influence their evolution are not well defined. We describe a novel molecular assay that reliably distinguishes cMCL and nnMCL using blood samples. We trained a 16-gene assay (L-MCL16 assay) on the NanoString platform using 19 purified leukemic samples. The locked assay was applied to an independent cohort of 70 MCL patients with leukemic presentation. The assay assigned 37% of cases to nnMCL and 56% to cMCL. nnMCL and cMCL differed in nodal presentation, lactate dehydrogenase, immunoglobulin heavy chain gene mutational status, management options, genomic complexity, and CDKN2A/ATM deletions, but the proportion with 17p/TP53 aberrations was similar in both subgroups. Sequential samples showed that assay prediction was stable over time. nnMCL had a better overall survival (OS) than cMCL (3-year OS 92% vs 69%; P 5 .006) from the time of diagnosis and longer time to first treatment. Genomic complexity and TP53/CDKN2A aberrations predicted for shorter OS in the entire series and cMCL, whereas only genomic complexity was associated with shorter time to first treatment and OS in nnMCL. In conclusion, the newly developed assay robustly recognizes the 2 molecular subtypes of MCL in leukemic samples. Its combination with genetic alterations improves the prognostic evaluation and may provide useful biological information for management decisions.
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U2 - 10.1182/blood-2018-03-838136
DO - 10.1182/blood-2018-03-838136
M3 - Article
C2 - 29769262
AN - SCOPUS:85051790136
SN - 0006-4971
VL - 132
SP - 413
EP - 422
JO - Blood
JF - Blood
IS - 4
ER -