Evidence map›Paper›PMID 39402215›Full record

ArticleLeukemia2025

Functional variant rs9344 at 11q13.3 regulates CCND1 expression in multiple myeloma with t(11;14).

Hongwei Tang, Huihuang Yan, Suganti Shivaram, Stacey Lehman, Neeraj Sharma, James Smadbeck, Cinthya Zepeda-Mendoza, Shulan Tian, Yan Asmann, Celine Vachon and 16 more

Abstract read
In one paragraph

Article in Leukemia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

26 authors.

Hongwei Tang *Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Huihuang Yan *Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0003-0756-2922
Suganti Shivaram *Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Stacey LehmanDivision of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Neeraj SharmaDivision of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-8229-3083
James SmadbeckCenter for Individualized Medicine-Biomarker Discovery, Mayo Clinic, Rochester, MN, USA.
Cinthya Zepeda-MendozaDivision of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Shulan TianDivision of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Yan AsmannDivision of Computational Biology, Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA.
Celine VachonDivision of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-1962-9322
Alexandre Gaspar MaiaDivision of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0001-8528-5575
Jonathan KeatsIntegrated Cancer Genomics, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA.ORCID 0000-0003-4375-7399
P Leif BergsagelDivision of Hematology, Department of Internal Medicine, Mayo Clinic, Scottsdale, AZ, USA.ORCID 0000-0003-1523-7388
Rafael FonsecaDivision of Hematology, Department of Internal Medicine, Mayo Clinic, Scottsdale, AZ, USA.ORCID 0000-0002-5938-3769
A Keith StewartPrincess Margaret Cancer Centre, Toronto, ON, Canada.
Joel-Sean HsuDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Richard K KandasamyDivision of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-0894-1222
Akhilesh PandeyDivision of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0001-9943-6127
Marcella A KaddouraDivision of Myeloma, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
Francesco MauraDivision of Myeloma, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.ORCID 0000-0002-5017-1620
Amit MitraDrug Discovery and Development, Auburn University, Auburn, AL, USA.ORCID 0000-0003-4046-7070
S Vincent RajkumarDivision of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0002-5862-1833
Shaji K KumarDivision of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0001-5392-9284
Eran ElhaikDepartment of Biology, Lund University, Lund, Sweden.
Esteban BraggioDivision of Hematology, Department of Internal Medicine, Mayo Clinic, Scottsdale, AZ, USA.ORCID 0000-0003-3860-4830
Linda B BaughnDivision of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. baughn.linda@mayo.edu.ORCID 0000-0001-5229-4897

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI AKHILESH PANDEY · 1985 to 2026
$151.3M
Project 4: Targeting Resistance to T-Cell Directed Therapy in Multiple MyelomaP50CA186781 · NCI · MAYO CLINIC ARIZONA · PI Peter Leif Bergsagel · 2015 to 2026
$25.5M
Mayo Clinic Center for Clinical ProteomicsU01CA271410 · NCI · MAYO CLINIC ROCHESTER · PI Rafael Fonseca, AKHILESH PANDEY · 2022 to 2026
$5.3M
Differences in Tumor Biology of Multiple Myeloma in Association with African AncestryR37CA272883 · NCI · MAYO CLINIC ROCHESTER · PI LINDA B BAUGHN · 2023 to 2026
$1.8M
NCI NIH HHS P30 CA015083NCI NIH HHS P50 CA186781NCI NIH HHS R37 CA272883NCI NIH HHS U01 CA271410U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (National Cancer Institute Division of Cancer Epidemiology and Genetics) R37CA272883
6 · The paper itself

Abstract

Multiple myeloma (MM) is a plasma cell (PC) malignancy characterized by cytogenetic abnormalities, such as t(11;14)(q13;q32), resulting in CCND1 overexpression. The rs9344 G allele within CCND1 is the most significant susceptibility allele for t(11;14). Sequencing data from 2 independent cohorts, CoMMpass (n = 698) and Mayo Clinic (n = 661), confirm the positive association between the G allele and t(11;14). Among 80% of individuals heterozygous for rs9344 with t(11;14), the t(11;14) event occurs on the G allele, demonstrating a biological preference for the G allele in t(11;14). Within t(11;14), the G allele is associated with higher CCND1 expression and elevated H3K27ac and H3K4me3. CRISPR/Cas9 mediated A to G conversion resulted in increased H3K27ac over CCND1 and elevated CCND1 expression. ENCODE ChIP-seq data supported a PAX5 binding site within the enhancer region covering rs9344, showing preferential binding to the G allele. Overexpression of PAX5 resulted in increased CCND1 expression. These results support the importance of rs9344 G enhancer in increasing CCND1 expression in MM.

Indexed as

Chromosomes, Human, Pair 11Chromosomes, Human, Pair 14Cyclin D1Multiple MyelomaTranslocation, GeneticAllelesGene Expression Regulation, NeoplasticHumansPolymorphism, Single NucleotideCCND1 protein, humanCyclin D1

Identifiers

PMID39402215
PMCPMC11717701

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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.