Evidence map›Paper›PMID 38386293›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024

Broad Next-Generation Integrated Sequencing of Myelofibrosis Identifies Disease-Specific and Age-Related Genomic Alterations.

Malathi Kandarpa, Dan Robinson, Yi-Mi Wu, Tingting Qin, Kristen Pettit, Qing Li, Gary Luker, Maureen Sartor, Arul Chinnaiyan, Moshe Talpaz

Open access · hybridAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.1field-weighted citation impact, top 9% of its field
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

12 citing papers in PubMed, 8 citations in OpenAlex.

  1. U2af1Leukemia · 2026
    Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Single-cell RNA sequencing of platelets: challenges and potential.Journal of thrombosis and thrombolysis · 2026
    Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
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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

10 authors at 1 institution in 1 country.

Malathi KandarpaDivision of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-0440-4964
Dan RobinsonMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan.ORCID 0000-0002-2337-7439
Yi-Mi WuMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan.ORCID 0000-0002-3789-4445
Tingting QinDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0003-3810-7578
Kristen PettitDivision of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.ORCID 0009-0007-3536-4137
Qing LiDivision of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-4982-1024
Gary LukerDepartment of Radiology, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-6832-2581
Maureen SartorDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-6155-5702
Arul ChinnaiyanMichigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan.ORCID 0000-0001-9282-3415
Moshe TalpazDivision of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0003-3361-3981
University of Michigan · US

Funding

Sequencing, Analysis, and Interpretation of SequencingUM1HG006508 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M, PIENTA, KENNETH J. · 2013 to 2016
$7.8M
NHGRI NIH HHS UM1 HG006508
6 · The paper itself

Abstract

purposeMyeloproliferative neoplasms (MPN) are characterized by the overproduction of differentiated myeloid cells. Mutations in JAK2, CALR, and MPL are considered drivers of Bcr-Abl-ve MPN, including essential thrombocythemia (ET), polycythemia vera (PV), prefibrotic primary myelofibrosis (prePMF), and overt myelofibrosis (MF). However, how these driver mutations lead to phenotypically distinct and/or overlapping diseases is unclear. EXPERIMENTAL

designTo compare the genetic landscape of MF to ET/PV/PrePMF, we sequenced 1,711 genes for mutations along with whole transcriptome RNA sequencing of 137 patients with MPN.

resultsIn addition to driver mutations, 234 and 74 genes were found to be mutated in overt MF (N = 106) and ET/PV/PrePMF (N = 31), respectively. Overt MF had more mutations compared with ET/PV/prePMF (5 vs. 4 per subject, P = 0.006). Genes frequently mutated in MF included high-risk genes (ASXL1, SRSF2, EZH2, IDH1/2, and U2AF1) and Ras pathway genes. Mutations in NRAS, KRAS, SRSF2, EZH2, IDH2, and NF1 were exclusive to MF. Advancing age, higher DIPSS, and poor overall survival (OS) correlated with increased variants in MF. Ras mutations were associated with higher leukocytes and platelets and poor OS. The comparison of gene expression showed upregulation of proliferation and inflammatory pathways in MF. Notably, ADGRL4, DNASE1L3, PLEKHGB4, HSPG2, MAMDC2, and DPYSL3 were differentially expressed in hematopoietic stem and differentiated cells.

conclusionsOur results illustrate that evolution of MF from ET/PV/PrePMF likely advances with age, accumulation of mutations, and activation of proliferative pathways. The genes and pathways identified by integrated genomics approach provide insight into disease transformation and progression and potential targets for therapeutic intervention.

Indexed as

High-Throughput Nucleotide SequencingMutationPrimary MyelofibrosisAdultAgedAged, 80 and overAge FactorsFemaleGene Expression ProfilingGenomicsHumansMaleMiddle AgedPolycythemia VeraTranscriptome

Identifiers

PMID38386293
PMCPMC11061602
OpenAlexW4392035498

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.