Evidence map›Paper›PMID 34355654›Full record

ArticleLeukemia & lymphoma2021

Pan-PI3Ki targets multiple B-ALL microenvironment interactions that fuel systemic and CNS relapse.

Sarah M Ridge, Andrew E Whiteley, Hisayuki Yao, Trevor T Price, Maegan L Brockman, Andrew S Murray, Brennan G Simon, Prioty Islam, Dorothy A Sipkins

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

Article in Leukemia & lymphoma, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 47% 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

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. Review
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

9 authors at 2 institutions in 3 countries.

Sarah M RidgeDepartment of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC, USA.
Andrew E WhiteleyDepartment of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC, USA.ORCID 0000-0002-0165-8395
Hisayuki YaoDepartment of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC, USA.
Trevor T PriceDepartment of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC, USA.
Maegan L BrockmanDepartment of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC, USA.
Andrew S MurrayDepartment of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC, USA.
Brennan G SimonDepartment of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC, USA.
Prioty IslamDepartment of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC, USA.
Dorothy A SipkinsDepartment of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC, USA.
Duke University · USKyushu University · JP

Funding

TRANSFUSION MEDICINE AND RELATED AREAST32HL007057 · NHLBI · DUKE UNIVERSITY · PI Gowthami M Arepally · 1985 to 2026
$10.6M
Defining and targeting a novel pathway for central nervous system leptomeningeal metastasisR01CA234580 · NCI · DUKE UNIVERSITY · PI SIPKINS, DOROTHY A · 2020 to 2024
$1.8M
Novel use of PI3K inhibition to prevent recurrence of B-cell acute lymphoblastic leukemiaR21CA263908 · NCI · DUKE UNIVERSITY · PI SIPKINS, DOROTHY A · 2021 to 2022
$409k
A DUAL ROLE OF INTEGRIN ALPHA-3 IN BREAST CANCER CNS METASTASIS & CHEMORESISTANCEF31CA257758 · NCI · DUKE UNIVERSITY · PI WHITELEY, ANDREW · 2021 to 2022
$73k
NCI NIH HHS F31 CA257758NCI NIH HHS R01 CA234580NCI NIH HHS R21 CA263908NHLBI NIH HHS T32 HL007057
6 · The paper itself

Abstract

The majority of adult patients with acute lymphoblastic leukemia (ALL) suffer relapse, and in patients with central nervous system (CNS) metastasis, prognosis is particularly poor. We recently demonstrated a novel route of ALL CNS metastasis dependent on PI3Kδ regulation of the laminin receptor integrin α6. B-ALL cells did not, however, rely on PI3Kδ signaling for growth. Here we show that broad targeting of PI3K isoforms can induce growth arrest in B-ALL, reducing systemic disease burden in mice treated with a single agent pan-PI3Ki, copanlisib. Moreover, we show that cellular stress activates PI3K/Akt-dependent survival pathways in B-ALL, exposing their vulnerability to PI3Kδ and pan-PI3Ki. The addition of a brief course of copanlisib to chemotherapy delivered the combined benefits of increased survival, decreased systemic disease, and reduced CNS metastasis. These data suggest the promising, multifaceted potential of pan-PI3Ki for B-ALL CNS prophylaxis, systemic disease control, and chemosensitization.

Indexed as

Central Nervous System NeoplasmsPrecursor Cell Lymphoblastic Leukemia-LymphomaAnimalsHumansMicePhosphatidylinositol 3-KinasesRecurrenceSignal TransductionTumor MicroenvironmentPhosphatidylinositol 3-Kinasesacute lymphoblastic leukemiachemosensitizationCNS relapsemicroenvironmentPI3K inhibition

Identifiers

PMID34355654
PMCPMC8722463
OpenAlexW3191864516

What OpenQuestion holds

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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.