Evidence map›Paper›PMID 40874324›Full record

ArticleHaematologica2026

C-C motif chemokine receptor-like 2 promotes the interferon-γ signaling response in myeloid neoplasms with erythroid differentiation and mutated

Nour Sabiha Naji, Sergiu Pasca, Theodora Chatzilygeroudi, Pablo Toledano-Sanz, Joseph Rimando, Yuju An, Yashvi Hemani, Brandy Perkins, Xinghan Zeng, Conover Talbot and 23 more

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Article in Haematologica, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Molecular and Clinical Insights intoInternational journal of molecular sciences · 2025
    Review
  6. Article
  7. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors.

Nour Sabiha NajiDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Sergiu PascaDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Theodora ChatzilygeroudiDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Pablo Toledano-SanzDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD.
Joseph RimandoDepartment of Hematology and Medical Oncology, Emory University School of Medicine, GA.
Yuju AnDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Yashvi HemaniDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Brandy PerkinsDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Xinghan ZengDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Conover TalbotInstitute for Basic Biomedical Sciences, Johns Hopkins University, Baltimore, MD.
Bogdan PaunDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Abdulmuez AbdulmalikDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Chen LossosDivision of Hematopathology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Tatianna R BoroninaDepartment of Biological Chemistry, Johns Hopkins University, Baltimore, MD.
Ilias SinanidisDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Panagiotis TsakiroglouDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Priyanka FernandesDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Christopher EstebDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Alexander J AmbinderDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Robert N ColeDepartment of Biological Chemistry, Johns Hopkins University, Baltimore, MD.
Rena XianDivision of Hematopathology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Ivana GojoDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Suman PaulDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Mark J LevisDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Amy E DeZernDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Leo LuznikHematology-Oncology Section, Baylor College of Medicine, Houston, TX.
Styliani KaranikaDivision of Infectious Diseases, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Linda S ResarDivision of Hematology, Department of Medicine, Johns Hopkins University, Baltimore, MD.
Richard J JonesDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Frederick BunzDepartment of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD.
Lukasz GondekDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Marios ArvanitisDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD.
Theodoros KarantanosDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland. tkarant1@jhmi.edu.

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI ALAN KEITH MEEKER · 1985 to 2026
$208.6M
Clonal Hematopoiesis in Healthy Individuals from Families with Early OnsetCoronary Artery DiseaseR01HL143818 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI BECKER, LEWIS C, RESAR, LINDA M S · 2019 to 2022
$3.3M
HMGA Chromatin Remodeling Proteins in Tumor Progression in Myeloproliferative Neoplasms (MPN)R01HL145780 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MOLITERNO, ALISON R, RESAR, LINDA M S · 2018 to 2021
$1.9M
TCR Targeting Antibodies for the Treatment of T cell CancersK08CA270403 · NCI · JOHNS HOPKINS UNIVERSITY · PI Suman Paul · 2022 to 2026
$1.1M
CCRL2 as a Regulator of Growth and Novel Target in Myelodysplastic SyndromeK08HL168777 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI Theodoros Karantanos · 2023 to 2026
$687k
Mechanisms of a therapeutic DNA vaccine targeting Mycobacterium tuberculosis persistersK08AI174959 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Styliani Karanika · 2024 to 2026
$603k
NCI NIH HHS K08 CA270403NCI NIH HHS P30 CA006973NHLBI NIH HHS K08 HL168777NHLBI NIH HHS R01 HL143818NHLBI NIH HHS R01 HL145780NIAID NIH HHS K08 AI174959
6 · The paper itself

Abstract

Patients with myeloid neoplasms with loss-of-function TP53 mutations and erythroid differentiation have poor outcomes, and a better understanding of disease biology is required. Upregulation of interferon-γ (IFN-γ) signaling has been associated with acute myeloid leukemia (AML) progression, selection of TP53 mutated clones and chemotherapy resistance, but its drivers remain unclear. In this study, we found that the surface receptor C-C motif chemokine receptor-like 2 (CCRL2) is over-expressed in AML with erythroid differentiation and TP53 mutations compared to other AML subtypes and healthy hematopoietic cells. CCRL2 knockout (KO) suppressed erythroleukemia growth in vitro and in vivo. Further proteomics and transcriptomics analysis revealed IFN-γ signaling response as the top CCRL2-regulated pathway in erythroleukemia. Our mechanistic studies support direct CCRL2-driven IFN-γ signaling upregulation without a clear effect of exogenous IFN-γ, through phosphorylation of STAT1, which is partially mediated by JAK2. CCRL2/IFN-γ signaling is up-regulated in erythroid leukemias, and TP53 mutated AML and appears to be directly induced by TP53 KO. Finally, CCRL2/IFN-γ signaling is associated with the transformation of pre-leukemic single-hit TP53 clones to multi-hit TP53 mutated AML, increased resistance to venetoclax and worse survival in AML. Overall, our findings support the view that CCRL2 is an essential driver of cell-autonomous IFN-γ signaling response in myeloid neoplasms with erythroid differentiation and TP53 mutations, and highlight CCRL2 as a relevant novel target for these neoplasms.

Indexed as

Erythroid CellsInterferon-gammaLeukemia, Myeloid, AcuteMutationSignal TransductionTumor Suppressor Protein p53AnimalsCell DifferentiationCell Line, TumorHumansJanus Kinase 2Leukemia, Erythroblastic, AcuteMiceSTAT1 Transcription FactorInterferon-gammaJanus Kinase 2STAT1 Transcription FactorTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID40874324
PMCPMC12862311

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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.