Evidence map›Paper›PMID 42160756›Full record

ArticleBlood advances2026

A PBD dimer-containing antibody-drug conjugate targeting CCRL2 for high-risk MDS/AML including TP53-mutated disease.

Nour Sabiha Naji, Taha Ahmedna, Xinghan Zeng, Yuju An, Yashvi Hemani, Brandy Perkins, Zanshe Thompson, Tushar D Nichakawade, Yanyan Wang, Bum Seok Lee and 16 more

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In one paragraph

Article in Blood advances, 2026. 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
–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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors.

Nour Sabiha NajiDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0009-0004-4761-7435
Taha AhmednaDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.
Xinghan ZengDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.
Yuju AnDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.
Yashvi HemaniDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.
Brandy PerkinsDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.
Zanshe ThompsonDivision of Hematology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD.
Tushar D NichakawadeLudwig Center and Lustgarten Laboratory, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD.
Yanyan WangDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0009-0002-1903-182X
Bum Seok LeeLudwig Center and Lustgarten Laboratory, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD.
Evangeline WatsonLudwig Center and Lustgarten Laboratory, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD.
Theodora ChatzilygeroudiDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0009-0003-6931-5828
Li LuoDivision of Hematology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-8680-4119
Bogdan PaunDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.
Melanie KlausnerDepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD.
Teodora SupeanuDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.
Ivana GojoDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0003-0312-3412
Gabriel GhiaurDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-3955-7944
Amy E DeZernDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.
Mark J LevisDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0003-0473-6982
Linda ResarDivision of Hematology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD.
Richard J JonesDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.
J David PeskeDivision of Hematopathology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0001-6314-6881
Styliani KaranikaDivision of Infectious Diseases, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0003-2387-6075
Suman PaulDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0001-9357-3702
Theodoros KarantanosDivision of Hematologic Malignancies and Bone Marrow Transplantation, Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.

Funding

T32: Predoctoral and Postdoctoral Training Program in Nanotechnology for Cancer ResearchT32CA153952 · NCI · JOHNS HOPKINS UNIVERSITY · PI Denis Wirtz · 2015 to 2026
$3.5M
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
NCI NIH HHS K08 CA270403NCI NIH HHS T32 CA153952NHLBI NIH HHS K08 HL168777
6 · The paper itself

Abstract

abstractPatients with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) with high-risk features including TP53 mutations have poor outcomes because of the lack of effective therapies. The atypical chemokine surface receptor C-C motif chemokine receptor-like 2 (CCRL2) is overexpressed in MDS and secondary AML compared with healthy hematopoietic cells, and we recently found that TP53-mutated MDS/AML and AML with erythroid features express the highest levels of this receptor across MDS/AML subtypes. To illustrate the therapeutic potential of CCRL2 as a therapeutic target, we developed an anti-CCRL2 antibody-drug conjugate (ADC) by conjugating an anti-CCRL2 antibody with the cytotoxic drug pyrrolobenzodiazepine (PBD), which causes DNA double-strand breaks, leading to cancer cell death. Anti-CCRL2 ADC demonstrated strong CCRL2-selective cytotoxicity associated with DNA damage against cell lines derived from patients with MDS/AML with TP53 mutations and erythroid features, surpassing the cytotoxic effects observed with gemtuzumab and PBD-conjugated anti-CD33 and anti-CD123 ADCs. It also induced apoptosis and suppressed the clonogenicity of primary MDS/AML bone marrow samples without affecting the survival, differentiation, and clonogenicity of healthy hematopoietic stem and progenitor cells. This agent also suppressed the leukemic growth of TP53-mutated MDS/AML cell line xenografts, improving mice survival and decreasing the leukemic burden in patient-derived TP53-mutated MDS/AML xenografts. In conclusion, our study introduces CCRL2 as a potential new therapeutic target in high-risk MDS/AML, including TP53-mutated subsets.

Indexed as

BenzodiazepinesImmunoconjugatesLeukemia, Myeloid, AcuteMutationMyelodysplastic SyndromesTumor Suppressor Protein p53AnimalsCell Line, TumorHumansMicePyrrolesXenograft Model Antitumor AssaysBenzodiazepinesImmunoconjugatesPyrrolespyrrolo(2,1-c)(1,4)benzodiazepineTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID42160756
PMCPMC13499191

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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.