Evidence map›Paper›PMID 38418394›Full record

ArticleJournal for immunotherapy of cancer2024

Paired single-B-cell transcriptomics and receptor sequencing reveal activation states and clonal signatures that characterize B cells in acute myeloid leukemia.

Shengnan Guo, Gopi S Mohan, Bofei Wang, Tianhao Li, Naval Daver, Yuting Zhao, Patrick K Reville, Dapeng Hao, Hussein A Abbas

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

9 citing papers in PubMed, 7 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

9 authors at 2 institutions in 2 countries.

Shengnan GuoSchool of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, China.ORCID 0000-0002-0867-9551
Gopi S MohanDepartment of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.ORCID 0000-0002-8204-9769
Bofei WangDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Tianhao LiSchool of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, China.
Naval DaverDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Yuting ZhaoSchool of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, China.
Patrick K RevilleDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA habbas@mdanderson.org dapeng.hao@gmail.com pkreville@mdanderson.org.
Dapeng HaoSchool of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, China habbas@mdanderson.org dapeng.hao@gmail.com pkreville@mdanderson.org.
Hussein A AbbasDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA habbas@mdanderson.org dapeng.hao@gmail.com pkreville@mdanderson.org.ORCID 0000-0003-2946-3562
The University of Texas MD Anderson Cancer Center · USHarbin Medical University · CN

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
NovaSeq6000S10OD024977 · OD · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HUFF, VICKI · 2018 to 2018
$995k
NCI NIH HHS P30 CA016672NIH HHS S10 OD024977
6 · The paper itself

Abstract

backgroundAcute myeloid leukemia (AML) is associated with a dismal prognosis. Immune checkpoint blockade (ICB) to induce antitumor activity in AML patients has yielded mixed results. Despite the pivotal role of B cells in antitumor immunity, a comprehensive assessment of B lymphocytes within AML's immunological microenvironment along with their interaction with ICB remains rather constrained.

methodsWe performed an extensive analysis that involved paired single-cell RNA and B-cell receptor (BCR) sequencing on 52 bone marrow aspirate samples. These samples included 6 from healthy bone marrow donors (normal), 24 from newly diagnosed AML patients (NewlyDx), and 22 from 8 relapsed or refractory AML patients (RelRef), who underwent assessment both before and after azacitidine/nivolumab treatment.

resultsWe delineated nine distinct subtypes of B cell lineage in the bone marrow. AML patients exhibited reduced nascent B cell subgroups but increased differentiated B cells compared with healthy controls. The limited diversity of BCR profiles and extensive somatic hypermutation indicated antigen-driven affinity maturation within the tumor microenvironment of RelRef patients. We established a strong connection between the activation or stress status of naïve and memory B cells, as indicated by AP-1 activity, and their differentiation state. Remarkably, atypical memory B cells functioned as specialized antigen-presenting cells closely interacting with AML malignant cells, correlating with AML stemness and worse clinical outcomes. In the AML microenvironment, plasma cells demonstrated advanced differentiation and heightened activity. Notably, the clinical response to ICB was associated with B cell clonal expansion and plasma cell function.

conclusionsOur findings establish a comprehensive framework for profiling the phenotypic diversity of the B cell lineage in AML patients, while also assessing the implications of immunotherapy. This will serve as a valuable guide for future inquiries into AML treatment strategies.

Indexed as

Leukemia, Myeloid, AcuteAzacitidineB-LymphocytesBone MarrowGene Expression ProfilingHumansTumor MicroenvironmentAzacitidineComputational BiologyGene Expression ProfilingImmune Checkpoint InhibitorsTumor Microenvironment

Identifiers

PMID38418394
PMCPMC10910691
OpenAlexW4392300865

What Socratic holds

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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 Socratic graph.