Evidence map›Paper›PMID 38555405›Full record

ArticleLeukemia2024

A complex interplay of intra- and extracellular factors regulates the outcome of fetal- and adult-derived MLL-rearranged leukemia.

Maria Jassinskaja, Sudip Ghosh, Joanna Watral, Mina Davoudi, Melina Claesson Stern, Ugarit Daher, Mohamed Eldeeb, Qinyu Zhang, David Bryder, Jenny Hansson

Open access · hybridAbstract read
In one paragraph

Article in Leukemia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed, 7 citations in OpenAlex.

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  4. Review
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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 2 countries.

Maria Jassinskaja *Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, SE-221 84, Lund, Sweden.
Sudip Ghosh *Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, SE-221 84, Lund, Sweden.
Joanna WatralLund Stem Cell Center, Department of Experimental Medical Science, Lund University, SE-221 84, Lund, Sweden.ORCID 0000-0003-0962-5114
Mina DavoudiLund Stem Cell Center, Department of Experimental Medical Science, Lund University, SE-221 84, Lund, Sweden.
Melina Claesson SternLund Stem Cell Center, Department of Experimental Medical Science, Lund University, SE-221 84, Lund, Sweden.
Ugarit DaherLund Stem Cell Center, Department of Experimental Medical Science, Lund University, SE-221 84, Lund, Sweden.ORCID 0000-0003-2821-6121
Mohamed EldeebLund Stem Cell Center, Department of Laboratory Medicine, Lund University, SE-221 84, Lund, Sweden.ORCID 0000-0002-8636-2189
Qinyu ZhangLund Stem Cell Center, Department of Laboratory Medicine, Lund University, SE-221 84, Lund, Sweden.ORCID 0000-0001-8292-938X
David BryderLund Stem Cell Center, Department of Laboratory Medicine, Lund University, SE-221 84, Lund, Sweden.ORCID 0000-0002-8761-4237
Jenny HanssonLund Stem Cell Center, Department of Experimental Medical Science, Lund University, SE-221 84, Lund, Sweden. jenny.hansson@med.lu.se.ORCID 0000-0001-9174-8089
Lund University · SE

Funding

Barncancerfonden (Swedish Childhood Cancer Foundation) PR2016-0148Barncancerfonden (Swedish Childhood Cancer Foundation) PR2022-0147Barncancerfonden (Swedish Childhood Cancer Foundation) TJ2106-0038Cancerfonden (Swedish Cancer Society) 22 2347 PjVetenskapsrådet (Swedish Research Council) 2015-03063Vetenskapsrådet (Swedish Research Council) 2019-01761Vetenskapsrådet (Swedish Research Council) 2021-00185Vetenskapsrådet (Swedish Research Council) 2023-03173
6 · The paper itself

Abstract

Infant and adult MLL1/KMT2A-rearranged (MLLr) leukemia represents a disease with a dismal prognosis. Here, we present a functional and proteomic characterization of in utero-initiated and adult-onset MLLr leukemia. We reveal that fetal MLL::ENL-expressing lymphomyeloid multipotent progenitors (LMPPs) are intrinsically programmed towards a lymphoid fate but give rise to myeloid leukemia in vivo, highlighting a complex interplay of intra- and extracellular factors in determining disease subtype. We characterize early proteomic events of MLL::ENL-mediated transformation in fetal and adult blood progenitors and reveal that whereas adult pre-leukemic cells are mainly characterized by retained myeloid features and downregulation of ribosomal and metabolic proteins, expression of MLL::ENL in fetal LMPPs leads to enrichment of translation-associated and histone deacetylases signaling proteins, and decreased expression of inflammation and myeloid differentiation proteins. Integrating the proteome of pre-leukemic cells with their secretome and the proteomic composition of the extracellular environment of normal progenitors highlights differential regulation of Igf2 bioavailability, as well as of VLA-4 dimer and its ligandome, upon initiation of fetal- and adult-origin leukemia, with implications for human MLLr leukemia cells' ability to communicate with their environment through granule proteins. Our study has uncovered opportunities for targeting ontogeny-specific proteomic vulnerabilities in in utero-initiated and adult-onset MLLr leukemia.

Indexed as

Myeloid-Lymphoid Leukemia ProteinAdultAnimalsFemaleFetusGene RearrangementHistone-Lysine N-MethyltransferaseHumansLeukemiaMiceOncogene Proteins, FusionProteomicsHistone-Lysine N-MethyltransferaseKMT2A protein, humanMLL-ENL oncoprotein, humanMyeloid-Lymphoid Leukemia ProteinOncogene Proteins, Fusion

Identifiers

PMID38555405
PMCPMC11073998
OpenAlexW4393334668

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.