About

Kathrin M. Bernt, MD, is an Associate Professor of Pediatrics (Oncology) and an Attending Physician in the Division of Pediatric Oncology at the Children's Hospital of Philadelphia. She is a member of the Abramson Cancer Center at the University of Pennsylvania. Her clinical expertise focuses on the care of patients with Pediatric Hematologic Malignancies. Her research aims to understand the molecular makeup of leukemia to develop targeted therapies, with a focus on epigenetics and transcriptional regulation. Her laboratory investigates molecular mechanisms in leukemia using various models, including genetically engineered murine models, retroviral murine models, cell lines, patient samples, and patient-derived xenografts. Her projects include studying IDH mutations in AML, the role of MN1 fusions and overexpression in leukemia, and the epigenetic abnormalities in inv(16) AML. She has contributed to understanding the chromatin pathways involved in leukemia and is involved in projects supported by organizations such as the NCI, Doris Duke Charitable Foundation, and Hyundai Hope on Wheels.

Research topics

• Genetics
• Biology
• Pathology
• Computer Science
• Medicine
• Computational biology
• Cancer research
• Bioinformatics
• World Wide Web
• Immunology
• Virology

Selected publications

• Supplementary Tables 1 - 27 from Molecular Plasticity Results in Oncofetal Reprogramming and Therapeutic Vulnerabilities in Juvenile Myelomonocytic Leukemia

  2026-03-04

  articleOpen access

  <p>Supplementary Tables file contains Supplementary Tables 1 - 27 providing detailed information about the samples and reagents used as well as information on epigenetic and transcriptional signatures.</p>

  PublisherDOI

• Data from Molecular Plasticity Results in Oncofetal Reprogramming and Therapeutic Vulnerabilities in Juvenile Myelomonocytic Leukemia

  2026-03-04

  articleOpen access

  <div>Abstract<p>Persistent fetal gene expression in childhood neoplasms is usually explained by a maturation block originating in the prenatal phase. In contrast, reactivation of fetal genes in adult malignancies is considered a consequence of oncofetal reprogramming (OFR) and is associated with aggressive disease. By reconstructing epigenetic ontogeny in juvenile myelomonocytic leukemia (JMML), we identified a postnatal maturation state of JMML stem cells with high transcriptional plasticity indicative of OFR in high-risk disease. Similarly, postnatal activation of oncogenic signaling by inducible <i>Ptpn11</i><sup><i>E76K</i></sup> mutation in mice triggered molecular plasticity and reactivation of fetal gene expression. Integrative multi-omics analysis revealed aberrant CD52 expression as a feature of high-risk JMML stem cells. Anti-CD52 treatment depleted JMML stem cells and blocked disease propagation in xenograft models. Our results challenge the prevailing maturation block model of pediatric leukemogenesis and establish RAS-associated stem cell plasticity as a determinant of OFR and potential therapeutic vulnerabilities in high-risk JMML.</p>Significance:<p>Persistent fetal gene expression in pediatric malignancies is considered a consequence of prenatal maturation blockade. In this study, we demonstrate that oncogenic <i>PTPN11</i> mutations enhance cellular plasticity. This leads to partial restoration of fetal molecular programs, creating new therapeutically exploitable vulnerabilities.</p><p><a href="https://aacrjournals.org/bloodcancerdiscov/article-abstract/doi/10.1158/2643-3230.BCD-26-0006" target="_blank"><i>See related commentary by Miao and Xu, pp. 168</i></a></p></div>

  PublisherDOI

• CD19 CAR T-cell Therapy in Infant B-ALL: Durable Remissions, Relapse Patterns, and Molecular Correlates

  Transplantation and Cellular Therapy · 2026-02-01

  article
  PublisherDOI

• CCR4 expression defines a targetable subset of T-cell acute lymphoblastic leukemia

  Blood Advances · 2026-02-11 · 1 citations

  articleOpen access

  ABSTRACT: Patients with relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) have a dismal prognosis largely mediated by nonsustained responses to chemotherapy and few targeted therapy options. Surface antigen targets in T-ALL include CD2, CD5, CD7, and CD38; however, ongoing clinical development of these targets is challenged by (1) T-cell fratricide during manufacturing, (2) T-cell depletion during treatment, and (3) high frequency of target-negative relapse. Here, we use a combination of flow cytometry, single-cell genomics, and bulk RNA sequencing to identify CC chemokine receptor type 4 (CCR4) as a novel surface target in T-ALL. We analyzed the T-ALL microenvironment from 40 patients treated on the AALL0434 clinical trial and identified a subpopulation of bone marrow-enriched CCR4+ FOXP3+ T-regulatory cells that express immune checkpoints (PD-1 and TIGIT) and could be targeted with anti-CCR4 therapy. Finally, we describe the preclinical efficacy of an anti-CCR4 chimeric antigen receptor T-cell therapy in in vitro and in vivo models, paving the way for future translational efforts in chemotherapy-refractory T-ALL.

  PublisherOA PDFDOI

• CRISPR-based functional genomics for dissecting therapeutic dependency in primary acute myeloid leukemia samples

  Molecular Cell · 2026-02-26

  articleOpen accessCorresponding

  Cancer functional genomics enables high-throughput target discovery and mechanistic investigation, yet its application has remained largely confined to mouse models and established human cancer cell lines. Direct functional interrogation of heterogeneous primary tumors offers a powerful opportunity to evaluate therapeutic targets and uncover cancer dependencies or resistance mechanisms. Here, we developed an optimized CRISPR-based platform for functional genomics in patient-derived xenograft and primary acute myeloid leukemia (AML) samples harboring diverse pathogenic mutations. Integrated in vitro and in vivo CRISPR-Cas9 knockout and CRISPR interference (CRISPRi) dropout screens validated known AML-biased targets and identified cis- regulatory elements essential for leukemic growth. Coupling pooled CRISPR perturbations with single-cell RNA sequencing (Perturb-seq) further resolved the perturbation-induced alterations in regulatory networks, cell cycle states, and cellular hierarchies in primary AML samples. Together, these studies establish a general and robust framework for leveraging CRISPR-based functional genomics to directly dissect cancer dependencies and cellular heterogeneity in primary AML patient samples. • Optimized CRISPR platform for genetic studies in primary AML samples • In vitro and in vivo CRISPR screens reveal shared and distinct AML dependencies • CRISPRi screens identify essential cis- regulatory elements in PDXs • Perturb-seq dissects regulatory networks and heterogeneity in primary AML cells Direct CRISPR functional genomics in primary patient samples holds promise for therapeutic target validation and discovery. Cao et al. develop an optimized CRISPR platform for genetic screening in primary acute myeloid leukemia samples. Integrated knockout, knockdown, and Perturb-seq screens dissect cancer vulnerabilities and cellular heterogeneity directly in patient-derived cells.

  PublisherDOI

• Supplementary Figures S1-S15 from Molecular Plasticity Results in Oncofetal Reprogramming and Therapeutic Vulnerabilities in Juvenile Myelomonocytic Leukemia

  2026-03-04

  articleOpen access

  <p>File containing Supplementary Figures S1-S15</p>

  PublisherDOI

• O53: Can integrated genomic analysis replace chromosomal analysis for the diagnosis of hematological malignancies: Addressing the shortage of cytogenetic technologists

  Genetics in Medicine Open · 2025-01-01

  articleOpen access

  Chromosomal analysis (CA) has been part of the standard care for patients with hematological malignancies since Dr. Nowell and colleague discovered the Philadelphia chromosome in chronic myelogenous leukemia in 1961. CA examines cancer-associated numerical and structural abnormalities at the single-cell level and has played a significant role in leukemia diagnosis, risk stratification, and treatment selection. However, the resolution of CA in detecting chromosomal rearrangements and copy number variations (CNVs) is limited.

  PublisherOA PDFDOI

• Combinatorial inhibition of LSD1 and Menin induces therapeutic differentiation in AML

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-11

  preprintOpen access

  Abstract Acute myeloid leukemia (AML) is characterized by differentiation arrest and uncontrolled proliferation. Differentiation therapy aims to treat AML by de-repressing latent myeloid maturation programs to induce cell cycle arrest and subsequent cell death. This approach is curative in the promyelocytic AML subtype, but has met with limited success in other subtypes. Genes such as LSD1 have emerged as intriguing non-APL AML differentiation therapy targets, but results as monoagents in clinical trials have been mixed. Here, we performed differentiation-specific CRISPR screens to identify targets whose inhibition synergizes with LSD1 inhibition to induce terminal differentiation of non-APL AML cells. Intriguingly, the MLL co-factor Menin scored as the top hit. Using cell lines, primary patient samples, and mouse AML models, we find that dual inhibition of LSD1 and Menin is a highly promising approach for differentiation therapy. Mechanistically, we determine that inhibition of Menin downregulates drivers of proliferation and stemness such as MEIS1, and inhibition of LSD1 induces inflammatory and interferon-related pro-myeloid differentiation expression programs. Surprisingly, we find that this combination is effective in selected AML models without mutations in MLL or NPM1, thus nominating dual inhibition of LSD1 and Menin as an attractive therapeutic approach for a mutationally diverse set of non-APL AMLs. Highlights Inhibition of LSD1 and Menin synergizes to induce differentiation of MLL-r and MLL-WT AMLs. Inhibition of Menin downregulates drivers of proliferation and stemness. Inhibition of LSD1 induces differentiation-associated inflammatory and interferon responses. LSD1 and Menin occupy different areas of the genome.

  PublisherDOI

• Longitudinal single-cell multiomic atlas of high-risk neuroblastoma reveals chemotherapy-induced tumor microenvironment rewiring

  Nature Genetics · 2025-04-14 · 23 citations

  articleOpen access

  High-risk neuroblastoma, a leading cause of pediatric cancer mortality, exhibits substantial intratumoral heterogeneity, contributing to therapeutic resistance. To understand tumor microenvironment evolution during therapy, we longitudinally profiled 22 patients with high-risk neuroblastoma before and after induction chemotherapy using single-nucleus RNA and ATAC sequencing and whole-genome sequencing. This revealed profound shifts in tumor and immune cell subpopulations after therapy and identified enhancer-driven transcriptional regulators of neuroblastoma neoplastic states. Poor outcome correlated with proliferative and metabolically active neoplastic states, whereas more differentiated neuronal-like states predicted better prognosis. Proportions of mesenchymal neoplastic cells increased after therapy and a high proportion correlated with a poorer chemotherapy response. Macrophages significantly expanded towards pro-angiogenic, immunosuppressive and metabolic phenotypes. We identified paracrine signaling networks and validated the HB-EGF-ERBB4 axis between macrophage and neoplastic subsets, which promoted tumor growth through the induction of ERK signaling. These findings collectively reveal intrinsic and extrinsic regulators of therapy response in high-risk neuroblastoma.

  PublisherOA PDFDOI

• Genome-wide association study of childhood B-cell acute lymphoblastic leukemia reveals novel African ancestry-specific susceptibility loci

  Nature Communications · 2025-10-22 · 1 citations

  articleOpen access

  Abstract B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignancy. Given racial/ethnic differences in incidence and outcomes, B-ALL genome-wide association studies among children of African ancestry are needed. Leveraging multi-institutional datasets with 840 African American children with B-ALL and 3360 controls, nine loci achieved genome-wide significance ( P < 5 × 10 −8 ) after meta-analysis. Two loci were established trans-ancestral susceptibility regions ( IKZF1 , ARID5B ), while the remaining novel loci were specific to African populations. Five-year overall survival among children carrying novel risk alleles was significantly worse (83% versus 96% in non-carriers, P = 4.8 × 10 −3 ). Novel risk variants were also associated with subtype-specific disease ( P < 0.05), including higher susceptibility for a subtype overrepresented in African American children ( TCF3-PBX1 ) and lower susceptibility for a subtype with excellent prognosis ( ETV6-RUNX1 ). Functional experiments revealed novel B-ALL risk variants had allele-specific differences in transcriptional activity ( P < 0.05) in B-cell and leukemia cell lines. These findings shed insights into ancestry-related differences in leukemogenesis and prognosis.

  PublisherOA PDFDOI

Recent grants

• H3K79 Methylation in Hematopoietic Stem Cell Development and MLL-Rearranged Leuk

  NIH · $660k · 2010–2016

• The role of H3K79 methylation in IDH-mutant leukemia

  NIH · $2.2M · 2017–2021

Frequent coauthors

• Simone S. Riedel

  Children's Hospital of Philadelphia

  79 shared

• Tobias Neff

  Merck & Co., Inc., Rahway, NJ, USA (United States)

  71 shared

• Scott A. Armstrong

  Boston Children's Hospital

  57 shared

• Jessica N. Haladyna

  55 shared

• Fatemeh Alikarami‬

  Children's Hospital of Philadelphia

  51 shared

• Kai Tan

  Children's Hospital of Philadelphia

  44 shared

• Junwei Shi

  University of Pennsylvania

  36 shared

• Liling Wan

  University of Pennsylvania

  35 shared

Labs

• Bernt LabPI

Education

• Fellow, Pediatric Hematology/Oncology

  Boston Children's Hospital

  2009

• R2-3 resident, Pediatrics

  Baylor College of Medicine

  2006

• MD, Humanmedizin

  Humboldt University / Free University

  1998