Evidence map›Paper›PMID 35418613›Full record

ArticleLeukemia2022

High expression level of ROR1 and ROR1-signaling associates with venetoclax resistance in chronic lymphocytic leukemia.

Emanuela M Ghia, Laura Z Rassenti, Michael Y Choi, Miguel Quijada-Álamo, Elvin Chu, George F Widhopf, Thomas J Kipps

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Leukemia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.6field-weighted citation impact, top 4% 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

24 citing papers in PubMed, 30 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

7 authors at 3 institutions in 2 countries.

Emanuela M GhiaMoores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0002-6060-6106
Laura Z RassentiMoores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA.
Michael Y ChoiMoores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA.
Miguel Quijada-ÁlamoUniversity of Salamanca, IBSAL, IBMCC-CSIC, Cancer Research Center, Salamanca, Spain.
Elvin ChuMoores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA.
George F WidhopfMoores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA.
Thomas J KippsMoores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA. tkipps@health.ucsd.edu.ORCID http://orcid.org/0000-0002-0064-4549
University of California San Diego · USUC San Diego Health System · USUniversidad de Salamanca · ES

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesse Nodora · 1985 to 2026
$124.9M
Non-canonical Wnt-Receptor Signaling and Targeted TherapiesR01CA236361 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KIPPS, THOMAS J · 2019 to 2023
$3.2M
Illumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600k
NCI NIH HHS P30 CA023100NCI NIH HHS R01 CA236361NIH HHS S10 OD026929
6 · The paper itself

Abstract

Although the BH3-mimetic venetoclax is highly cytotoxic for chronic lymphocytic leukemia (CLL) cells, some patients with CLL fail to clear minimal residual disease (MRD). We examined the CLL cells of seven such patients (CLL1-7) and found each had high-level expression of ROR1. By examining the CLL cells from such patients prior to therapy at SC1 and then more than 1 year later (Sample Collection 2 (SC2)), when they had progressive increases in MRD despite continued venetoclax therapy, we found the levels of ROR1 expressed on CLL cells at SC2 were significantly higher than that on CLL cells collected at SC1. At SC2, we also observed upregulation of genes induced by Wnt5a-induced ROR1 signaling, including BCL2L1. Transduction of the CLL-cell-line MEC1 to express ROR1 enhanced expression of target genes induced by ROR1-signaling, increased expression of BCL-XL, and enhanced resistance to venetoclax, even in MEC1 made to express mutant forms of BCL2, which are associated with venetoclax resistance. Treatment of primary CLL cells with Wnt5a also increased their resistance to venetoclax, an effect that could be inhibited by the anti-ROR1 mAb (UC-961, zilovertamab). Collectively, these studies indicate that Wnt5a-induced ROR1-signaling can enhance resistance to venetoclax therapy.

Indexed as

Leukemia, Lymphocytic, Chronic, B-CellBridged Bicyclo Compounds, HeterocyclicHumansReceptor Tyrosine Kinase-like Orphan ReceptorsSulfonamidesBridged Bicyclo Compounds, HeterocyclicReceptor Tyrosine Kinase-like Orphan ReceptorsROR1 protein, humanSulfonamidesvenetoclax

Identifiers

PMID35418613
PMCPMC9162914
OpenAlexW4224038236

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.