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

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          Publisher's Note: There is a [Related article:] Blood Commentary on this article in this issue.

          Key Points

          • A new molecular assay identifies conventional and leukemic nonnodal MCL with differing clinicobiological features.

          • The integration of the novel assay with genetic alterations identifies subsets of MCL patients with different management and outcome.


          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 = .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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          Author and article information

          American Society of Hematology (Washington, DC )
          26 July 2018
          16 May 2018
          26 July 2019
          : 132
          : 4
          : 413-422
          [1 ]Institute for Biomedical Research August Pi i Sunyer, Barcelona, Spain;
          [2 ]Centro de Investigación Biomédica en Red de Cáncer, Madrid, Spain;
          [3 ]Hematopathology Unit-Laboratory of Pathology, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain;
          [4 ]Hematology Department, Hospital Clinic of Barcelona, Barcelona, Spain;
          [5 ]Pathology Department and
          [6 ]Hematology Department, IMIM-Hospital del Mar, Barcelona, Spain;
          [7 ]Servei d'Hematologia, Hospital Mútua de Terrassa, Terrassa, Spain;
          [8 ]Institute of Pathology, University of Würzburg, Würzburg, Germany;
          [9 ]Comprehensive Cancer Center Mainfranken, Würzburg, Germany;
          [10 ]Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD;
          [11 ]Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada;
          [12 ]Department of Pathology, Toronto General Hospital, Toronto, ON, Canada;
          [13 ]Department of Clinical Pathology, Robert-Bosch-Krankenhaus and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany; and
          [14 ]Department of Pathology, Mayo Clinic, Scottsdale, AZ
          Author notes

          L.M.R., S.B., and E.C. contributed equally to this study.

          PMC6071558 PMC6071558 6071558 2018/838136
          © 2018 by The American Society of Hematology
          Page count
          Pages: 10
          Funded by: National Institutes of Health;
          Lymphoid Neoplasia


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