Evidence map›Paper›PMID 37989729›Full record

ArticleNature communications2023

Targetable lesions and proteomes predict therapy sensitivity through disease evolution in pediatric acute lymphoblastic leukemia.

Amanda C Lorentzian, Jenna Rever, Enes K Ergin, Meiyun Guo, Neha M Akella, Nina Rolf, C James Lim, Gregor S D Reid, Christopher A Maxwell, Philipp F Lange

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.3field-weighted citation impact, top 10% 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

6 citing papers in PubMed, 10 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 2 institutions in 1 country.

Amanda C LorentzianDepartment of Pediatrics, University of British Columbia, Vancouver, Canada.
Jenna ReverDepartment of Pediatrics, University of British Columbia, Vancouver, Canada.ORCID 0000-0001-8889-2063
Enes K ErginMichael Cuccione Childhood Cancer Research Program at the BC Children's Hospital Research Institute, Vancouver, Canada.ORCID 0000-0001-9810-7399
Meiyun GuoDepartment of Pediatrics, University of British Columbia, Vancouver, Canada.
Neha M AkellaDepartment of Pediatrics, University of British Columbia, Vancouver, Canada.
Nina RolfDepartment of Pediatrics, University of British Columbia, Vancouver, Canada.ORCID 0000-0002-4531-2994
C James LimDepartment of Pediatrics, University of British Columbia, Vancouver, Canada.ORCID 0000-0001-6381-7585
Gregor S D ReidDepartment of Pediatrics, University of British Columbia, Vancouver, Canada.ORCID 0000-0002-7567-3424
Christopher A MaxwellDepartment of Pediatrics, University of British Columbia, Vancouver, Canada. cmaxwell@bcchr.ca.ORCID 0000-0002-0713-7136
Philipp F LangeMichael Cuccione Childhood Cancer Research Program at the BC Children's Hospital Research Institute, Vancouver, Canada. philipp.lange@ubc.ca.ORCID 0000-0003-1171-5864
University of British Columbia · CAUniversity of British Columbia Hospital · CA

Funding

Canada Research Chairs (Chaires de recherche du Canada) CRC-RS 950-230867Gouvernement du Canada | Instituts de Recherche en Santé du Canada | CIHR Skin Research Training Centre (Skin Research Training Centre) PJF-169655Gouvernement du Canada | Instituts de Recherche en Santé du Canada | CIHR Skin Research Training Centre (Skin Research Training Centre) PJT-169190Michael Smith Foundation for Health Research (MSFHR) 16442
6 · The paper itself

Abstract

Childhood acute lymphoblastic leukemia (ALL) genomes show that relapses often arise from subclonal outgrowths. However, the impact of clonal evolution on the actionable proteome and response to targeted therapy is not known. Here, we present a comprehensive retrospective analysis of paired ALL diagnosis and relapsed specimen. Targeted next generation sequencing and proteome analysis indicate persistence of actionable genome variants and stable proteomes through disease progression. Paired viably-frozen biopsies show high correlation of drug response to variant-targeted therapies but in vitro selectivity is low. Proteome analysis prioritizes PARP1 as a pan-ALL target candidate needed for survival following cellular stress; diagnostic and relapsed ALL samples demonstrate robust sensitivity to treatment with two PARP1/2 inhibitors. Together, these findings support initiating prospective precision oncology approaches at ALL diagnosis and emphasize the need to incorporate proteome analysis to prospectively determine tumor sensitivities, which are likely to be retained at disease relapse.

Indexed as

Precursor Cell Lymphoblastic Leukemia-LymphomaProteomeChildHumansMutationPrecision MedicineProspective StudiesRecurrenceRetrospective StudiesProteome

Identifiers

PMID37989729
PMCPMC10663560
OpenAlexW4388845885

What Socratic 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 Socratic graph.