Evidence map›Paper›PMID 41193463›Full record

ArticleNature communications2025

Functional genomics and tumor microenvironment analysis reveal prognostic biological subtypes in Mantle cell lymphoma.

Sunandini Sharma, Roshia Ali, Alyssa Bouska, Dylan Jochum, Meghana Kesireddy, Simeon Mahov, Joseph Lownik, Weiwei Zhang, Waseem Lone, Mahfuza Afroz Soma and 29 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Trial
  2. [Advances in single cell omics applications in mantle cell lymphoma].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026
    Review
  3. Review
  4. Journal of clinical medicine · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

39 authors.

Sunandini Sharma *Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA.
Roshia Ali *Division of Oncology & Hematology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Alyssa Bouska *Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA.ORCID http://orcid.org/0000-0003-1324-6678
Dylan JochumDepartment of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA.ORCID http://orcid.org/0000-0003-2750-6741
Meghana KesireddyDivision of Oncology & Hematology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Simeon MahovDivision of Hematology and Cellular Therapy, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Joseph LownikPathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Weiwei ZhangDepartment of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA.
Waseem LoneDepartment of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA.
Mahfuza Afroz SomaDepartment of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA.
Alicia GamboaDivision of Hematology and Cellular Therapy, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Vaishnavi DevarakondaDivision of Hematology and Cellular Therapy, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Dalia El-GamalEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.ORCID http://orcid.org/0000-0002-1083-8283
Atqiya FarihaDivision of Oncology & Hematology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Adnan MansoorDepartment of Pathology and Laboratory Medicine, University of Calgary, Calgary, Canada.
Douglas StewartDepartments of Oncology and Medicine, University of Calgary, Calgary, Canada.
Peter MartinDivision of Hematology and Oncology, Weill Cornell Medical College, New York, NY, USA.
Brian K LinkDepartment of Internal Medicine, University of Iowa Hospitals & Clinics, Iowa City, Iowa, USA.
Ranjana H AdvaniDivision of Oncology, Stanford Cancer Institute, Stanford, CA, USA.
Paul M BarrDepartment of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Andre H GoyJohn Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
Amitkumar MehtaO'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.
Manali KamdarDivision of Hematology, University of Colorado, Denver, CO, USA.
Deborah M StephensHuntsman Cancer Institute at the University of Utah, Salt Lake City, UT, USA.
Veronika BachanovaDivision of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minnesota, MN, USA.
Lynette SmithDepartment of Biostatistics, University of Nebraska Medical Center, Omaha, NE, USA.
Ryan MorinDepartment of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.ORCID http://orcid.org/0000-0003-2932-7800
Prasath PararajalingamDepartment of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.ORCID http://orcid.org/0000-0003-3945-3552
Matthew A LunningDivision of Oncology & Hematology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Kai FuDepartment of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA.
Dennis WeisenburgerDepartment of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA.
Wing C ChanDepartment of Pathology, City of Hope National Medical Center, Duarte, CA, USA.ORCID http://orcid.org/0000-0002-6243-6008
Joseph KhouryDepartment of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA.ORCID http://orcid.org/0000-0003-2621-3584
Timothy C GreinerDepartment of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA.
Julie M VoseDivision of Oncology & Hematology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.ORCID http://orcid.org/0000-0003-1015-7434
Akil MerchantDivision of Hematology and Cellular Therapy, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-7472-822X
Chengfeng BiDivision of Oncology & Hematology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA. andy.bi@unmc.edu.ORCID http://orcid.org/0000-0001-5375-7515
Javeed IqbalDepartment of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA. jiqbal@unmc.edu.ORCID http://orcid.org/0000-0003-3668-0629
North American Mantle Cell Lymphoma Project (NAMCLP)

Funding

UNMC/EPPLEY CANCER CENTER SUPPORT GRANTP30CA036727 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI James Eudy · 1985 to 2026
$55.0M
Preclinical Models and Therapeutics CoreP01CA229100 · NCI · MAYO CLINIC ARIZONA · PI INGHIRAMI, GIORGIO · 2018 to 2022
$10.2M
Spatially resolved, single cell biomarkers of B cell lymphomaR01CA266544 · NCI · CEDARS-SINAI MEDICAL CENTER · PI Akil Merchant · 2022 to 2026
$3.2M
The Role of the CBFB-MYH11 Complex in Leukemia MaintenanceR01CA244900 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI HYDE, RICIA KATHERINE · 2020 to 2024
$1.9M
NCI NIH HHS P01 CA229100NCI NIH HHS P30 CA036727NCI NIH HHS R01 CA244900NCI NIH HHS R01 CA266544
6 · The paper itself

Abstract

Mantle cell lymphoma (MCL) is a genetically and clinically heterogeneous B-cell malignancy. We studied two MCL cohorts with differing treatment patterns: one enriched for immunochemotherapy, the other for chemotherapy alone. TP53 alterations are consistently associated with poor prognosis, whereas ATM mutations correlate with improved outcomes following rituximab-based chemotherapy. Based on recurrent genetic events, six clusters are identified and refined into three prognostic groups: high-risk (TP53 mutations and deletions at 17p13.3, 13q14.2, and 19p13.3), intermediate-risk (ATM and epigenetic regulator mutations, or gains at 8q/17q/15q), and low-risk (lacking TP53 alterations, rare ATM mutations without 11q deletions, gains at 3q, deletions at 6q). Transcriptomic analysis reveals enrichment of proliferation, metabolism-promoting gene signatures in high-risk; angiogenesis and NOTCH signaling in intermediate-risk; and proinflammatory-related (i.e., IFNα, TNFα) in low-risk MCLs. Multi-proteomic spatial profiling using imaging mass cytometry (IMC) demonstrates enrichment of CD4⁺ T cells with high expression of exhaustion markers and a dominant population of myeloid cells skewed toward an M2-like phenotype. Spatially, TP53-perturbed MCLs are immune-infiltrated yet exhausted, while ATM-perturbed cases remain immune-cold with dense tumors. Functional analysis shows that p53 represses BCR signaling through PTPN6 activation. Collectively, these findings highlight distinct molecular and immune landscapes and reveal therapeutic vulnerabilities in high-risk TP53-perturbed MCL.

Indexed as

Lymphoma, Mantle-CellTumor MicroenvironmentAgedAtaxia Telangiectasia Mutated ProteinsFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenomicsHumansMaleMiddle AgedMutationPrognosisRituximabTumor Suppressor Protein p53Ataxia Telangiectasia Mutated ProteinsATM protein, humanRituximabTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID41193463
PMCPMC12589501

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.