A gene signature that distinguishes conventional and leukemic nonnodal mantle cell lymphoma helps predict outcome

Guillem Clot, Pedro Jares, Eva Giné, Alba Navarro, Cristina Royo, Magda Pinyol, David Martín-Garcia, Santiago Demajo, Blanca Espinet, Antonio Salar, Ana Ferrer, Ana Muntañola, Marta Aymerich, Hilka Rauert-Wunderlich, Elaine S. Jaffe, Joseph M. Connors, Randy D. Gascoyne, Jan Delabie, Armando López-Guillermo, German OttGeorge W. Wright, Louis M. Staudt, Andreas Rosenwald, David W. Scott, Lisa Rimsza, Sílvia Beà, Elías Campo

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)413-422
Number of pages10
JournalBlood
Volume132
Issue number4
DOIs
StatePublished - Jul 26 2018

Fingerprint

Mantle-Cell Lymphoma
Assays
Genes
Survival
Aberrations
Immunoglobulin Heavy Chain Genes
Information Management
Immunoglobulin Heavy Chains
L-Lactate Dehydrogenase
Automatic teller machines
B-Lymphocytes
Blood
Cells
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Clot, G., Jares, P., Giné, E., Navarro, A., Royo, C., Pinyol, M., ... Campo, E. (2018). A gene signature that distinguishes conventional and leukemic nonnodal mantle cell lymphoma helps predict outcome. Blood, 132(4), 413-422. https://doi.org/10.1182/blood-2018-03-838136

A gene signature that distinguishes conventional and leukemic nonnodal mantle cell lymphoma helps predict outcome. / Clot, Guillem; Jares, Pedro; Giné, Eva; Navarro, Alba; Royo, Cristina; Pinyol, Magda; Martín-Garcia, David; Demajo, Santiago; Espinet, Blanca; Salar, Antonio; Ferrer, Ana; Muntañola, Ana; Aymerich, Marta; Rauert-Wunderlich, Hilka; Jaffe, Elaine S.; Connors, Joseph M.; Gascoyne, Randy D.; Delabie, Jan; López-Guillermo, Armando; Ott, German; Wright, George W.; Staudt, Louis M.; Rosenwald, Andreas; Scott, David W.; Rimsza, Lisa; Beà, Sílvia; Campo, Elías.

In: Blood, Vol. 132, No. 4, 26.07.2018, p. 413-422.

Research output: Contribution to journalArticle

Clot, G, Jares, P, Giné, E, Navarro, A, Royo, C, Pinyol, M, Martín-Garcia, D, Demajo, S, Espinet, B, Salar, A, Ferrer, A, Muntañola, A, Aymerich, M, Rauert-Wunderlich, H, Jaffe, ES, Connors, JM, Gascoyne, RD, Delabie, J, López-Guillermo, A, Ott, G, Wright, GW, Staudt, LM, Rosenwald, A, Scott, DW, Rimsza, L, Beà, S & Campo, E 2018, 'A gene signature that distinguishes conventional and leukemic nonnodal mantle cell lymphoma helps predict outcome', Blood, vol. 132, no. 4, pp. 413-422. https://doi.org/10.1182/blood-2018-03-838136
Clot, Guillem ; Jares, Pedro ; Giné, Eva ; Navarro, Alba ; Royo, Cristina ; Pinyol, Magda ; Martín-Garcia, David ; Demajo, Santiago ; Espinet, Blanca ; Salar, Antonio ; Ferrer, Ana ; Muntañola, Ana ; Aymerich, Marta ; Rauert-Wunderlich, Hilka ; Jaffe, Elaine S. ; Connors, Joseph M. ; Gascoyne, Randy D. ; Delabie, Jan ; López-Guillermo, Armando ; Ott, German ; Wright, George W. ; Staudt, Louis M. ; Rosenwald, Andreas ; Scott, David W. ; Rimsza, Lisa ; Beà, Sílvia ; Campo, Elías. / A gene signature that distinguishes conventional and leukemic nonnodal mantle cell lymphoma helps predict outcome. In: Blood. 2018 ; Vol. 132, No. 4. pp. 413-422.
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abstract = "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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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

AU - Beà, Sílvia

AU - Campo, Elías

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.

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