Evidence map›Paper›PMID 27060176›Full record

ArticleJournal of clinical pathology2016

Dysregulation of the intrinsic apoptotic pathway mediates megakaryocytic hyperplasia in myeloproliferative neoplasms.

Jacques A J Malherbe, Kathryn A Fuller, Bob Mirzai, Simon Kavanagh, Chi-Chiu So, Ho-Wan Ip, Belinda B Guo, Cecily Forsyth, Rebecca Howman, Wendy N Erber

Open access · hybridAbstract read
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In one paragraph

Article in Journal of clinical pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.0field-weighted citation impact, top 23% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

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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 5 institutions in 3 countries.

Jacques A J MalherbeSchool of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia.
Kathryn A FullerSchool of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia PathWest Laboratory Medicine, Nedlands, Western Australia, Australia.
Bob MirzaiSchool of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia PathWest Laboratory Medicine, Nedlands, Western Australia, Australia.
Simon KavanaghSchool of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia PathWest Laboratory Medicine, Nedlands, Western Australia, Australia.
Chi-Chiu SoDepartment of Pathology, Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong.
Ho-Wan IpDepartment of Pathology & Clinical Biochemistry, Queen Mary Hospital, Hong Kong, Hong Kong.
Belinda B GuoSchool of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia.
Cecily ForsythJarrett Street Specialist Centre, North Gosford, New South Wales, Australia.
Rebecca HowmanPathWest Laboratory Medicine, Nedlands, Western Australia, Australia.
Wendy N ErberSchool of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia PathWest Laboratory Medicine, Nedlands, Western Australia, Australia.
University of Western Australia · AUPathwest Laboratory Medicine · AUGosford Hospital · AUQueen Mary Hospital · CNUniversity of Hong Kong · HK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsMegakaryocyte expansion in myeloproliferative neoplasms (MPNs) is due to uncontrolled proliferation accompanied by dysregulation of proapoptotic and antiapoptotic mechanisms. Here we have investigated the intrinsic and extrinsic apoptotic pathways of megakaryocytes in human MPNs to further define the mechanisms involved.

methodsThe megakaryocytic expression of proapoptotic caspase-8, caspase-9, Diablo, p53 and antiapoptotic survivin proteins was investigated in bone marrow specimens of the MPNs (n=145) and controls (n=15) using immunohistochemistry. The megakaryocyte percentage positivity was assessed by light microscopy and correlated with the MPN entity, JAK2

resultsThe proportion of megakaryocytes in the MPNs expressing caspase-8, caspase-9, Diablo, survivin and p53 was significantly greater than controls. A greater proportion of myeloproliferative megakaryocytes expressed survivin relative to its reciprocal inhibitor, Diablo. Differences were seen between myelofibrosis, polycythaemia vera and essential thrombocythaemia for caspase-9 and p53. CALR-mutated cases had greater megakaryocyte p53 positivity compared to those with the JAK2

conclusionsDisruptions targeting the intrinsic apoptotic cascade promote megakaryocyte hyperplasia and thrombocytosis in the MPNs. There is progressive dysfunction of apoptosis as evidenced by the marked reduction in proapoptotic caspase-9 and accumulation of p53 in myelofibrosis. The dysfunction of caspase-9, which is necessary for proplatelet formation, may be the mechanism for the excess thrombocytosis associated with CALR mutations. Survivin seems to be the key protein mediating the megakaryocyte survival signature in the MPNs and is a potential therapeutic target.

Indexed as

APOPTOSISIMMUNOHISTOCHEMISTRYMYELOPROLIFERATIVE DISEASE

Identifiers

PMID27060176
PMCPMC5136711
OpenAlexW2323985047

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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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.