About

Kevin B. Johnson, M.D. is a Penn Integrates Knowledge University Professor with joint appointments in the Department of Biostatistics, Epidemiology, and Informatics in the Perelman School of Medicine and the Department of Computer and Information Science in the School of Engineering and Applied Science. He also holds a secondary appointment at the Annenberg School for Communication and serves as vice president for applied informatics in the University of Pennsylvania Health System, as well as a professor of pediatrics at the Children’s Hospital of Philadelphia. Johnson received his M.D. from Johns Hopkins Hospital and his M.S. in Medical Informatics from Stanford University. His career includes roles as Pediatric Chief Resident at Johns Hopkins, faculty positions in Pediatrics and Biomedical Information Sciences at Johns Hopkins, and a tenure at Vanderbilt University before joining Penn in 2021. He is a board-certified Pediatrician and is recognized as an internationally-respected developer and evaluator of clinical information technology. His research focuses on developing and promoting the adoption of clinical information systems to improve patient safety and adherence to practice guidelines, as well as exploring the use of advanced computer technologies in medicine. Johnson directed the development of evidence-based pediatric care guidelines at Johns Hopkins and has been principal investigator on numerous grants. He has authored over 150 publications and book chapters, and has received awards including the Robert Wood Johnson Foundation’s Harold Amos Medical Faculty Development Award and the American Academy of Pediatrics Byron B. Oberst Award. He was elected to the American College of Medical Informatics, The Academic Pediatric Society, and the National Academy of Medicine, and has held leadership roles within major medical informatics and pediatrics organizations.

Research topics

• Computer Science
• Medicine
• Biology
• Bioinformatics
• Cancer research
• Pathology
• Internal medicine
• Genetics
• Computational biology

Selected publications

• SPEN loss drives extra-follicular diffuse large B cell lymphoma with female-specific lethality and therapeutic vulnerabilities

  Cancer Discovery · 2026-04-21

  article

  Diffuse large B-cell lymphomas (DLBCL) are genetically and phenotypically heterogeneous, making diagnosis and treatment challenging. Current models suggest DLBCL derive from follicular B cells engaged in adaptive immune responses. By studying co-occurring truncating mutations in SPEN and NOTCH2 in the BN2-DLBCL subtype, our data suggest a previously unrecognized extra-follicular trajectory. Using animal models and human specimens, we find this cooperative mutational axis supports expansion of putative clonal precursors with features of marginal zone, memory and a distinct, autoimmune B-cell-like state. This trajectory is associated with sex-biased outcomes: female patients and mice exhibit reduced survival compared to males in our cohorts. Further analysis links this disparity to enhanced X-chromosome-linked expression and functionality of toll-like receptor signaling. We show that IRAK inhibition represents a potential sex-specific therapeutic strategy in preclinical models. These findings support a distinct developmental origin for BN2-DLBCL and identify a high-risk female population with actionable targets for precision therapy.

  PublisherDOI

• Table S5 from The FBXO45–GEF-H1 Axis Controls Germinal Center Formation and B-cell Lymphomagenesis

  2025-04-02

  preprintOpen accessSenior author

  <p>Supplementary Table S5, FISH analysis to identify copy number variations (CNV) affecting genes of interest within the corresponding genomic loci.</p>

  PublisherDOI

• Quantitative real-time polymerase chain reaction coupled with high-resolution melting (HRM) for simultaneous detection and quantification of four isoforms of BCR::ABL1

  Blood · 2025-11-03

  articleOpen accessSenior author

  Abstract Background The diagnosis and management of chronic myeloid leukemia (CML) critically rely on detecting and serially quantifying BCR::ABL1. The three major transcript variants are e1a2/e1a3 (p190), e13a2/e14a2 (p210), and e19a2/e19a3 (p230). Atypical transcripts have also been described, including e13a3/e14a3 (p203), which has been anecdotally linked to asciminib resistance. Currently, no clinical assay simultaneously detects multiple BCR::ABL1 isoforms; each isoform requires a separate analysis, which is labor-intensive and cost-inefficient. Consequently, baseline testing is typically limited to p210 and p190, without reflex testing for p230 or atypical isoforms if either is detected. This practice risks missing cases driven by p230 or atypical isoforms when these are co-expressed with low-level p190 or p210. Furthermore, standard monitoring focuses exclusively on baseline transcripts, potentially overlooking emerging novel isoforms during disease evolution, thereby falsely suggesting disease stability or remission and delaying timely therapeutic adjustments. Finally, the prevalence and significance of p203 remain unclear, partly because most primer sets fail to amplify the relevant ABL1 breakpoints. Methods To address these challenges, we developed a simple assay known as BloodHound to simultaneously detect and quantify four clinically relevant BCR::ABL1 transcripts (p190, p210, p230, and p203). This assay leverages real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and high-resolution melting (HRM) technologies, achieving a limit of detection of 0.001%, 99.9% sensitivity, and > 99% specificity when validated against droplet digital PCR and Sanger sequencing. To evaluate the clinical utility of this assay, we characterized the distribution and co-expression of the four transcripts in 895 samples, including peripheral blood (n = 846) and bone marrow (n = 49), from patients with suspected (n = 566), established (n = 296), relapsed (n = 32) CML, or unknown status (n = 1). Results were confirmed by Sanger sequencing as the gold standard. Results Overall, 187/895 samples (20.9%) were BCR::ABL1-positive. Positivity rates were 3.5% (20/566) in patients evaluated for suspected CML, 33.1% (98/296) in established CML under monitoring, and 100% (32/32) in relapsed disease. As expected, p210 alone predominated (161/187, 86.1% of positives), while p190 alone (2/187, 1.1%) and p230 alone (1/187, 0.5%) were rare, and p203 was not detected. Co-expression of p190 and p210 was more frequent than historically appreciated (23/187, 12.3%), particularly in baseline diagnostic specimens (25.0%). The results showed 100% concordance with Sanger sequencing. Quantitatively, p210 levels were markedly higher than p190 when co-expressed (median p210:p190 ratio = 2,152). Quantitative values obtained with our approach correlated tightly with the standardized Qiagen ipsogen IS assay (r = 0.998; median absolute difference = 0.02%). Conclusion The BloodHound assay is sensitive and accurate, and by simultaneously quantifying four clinically significant BCR::ABL1 transcripts, it has the potential to significantly streamline clinical workflows, enhance diagnostic precision, and offer deeper insights into CML clonal dynamics. Both RT-qPCR and HRM are compatible with standard laboratory equipment, facilitating implementation and widespread clinical adoption.

  PublisherOA PDFDOI

• HLA-I aberrations in cutaneous T-cell lymphoma

  Blood · 2025-01-16

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Supplementary Figures S1-S13 from The FBXO45–GEF-H1 Axis Controls Germinal Center Formation and B-cell Lymphomagenesis

  2025-04-02

  preprintOpen accessSenior author

  <p>Supplementary Data file shows all the supplementary figures, figure legends and supplementary table legends.</p>

  PublisherDOI

• Spen loss drives extra-follicular diffuse large B cell lymphoma with female-specific lethality and TLR pathway therapeutic vulnerabilities

  Blood · 2025-11-03

  articleOpen access

  Abstract Diffuse large B cell lymphomas (DLBCL) are the most common lymphoid malignancies in adults. Despite advances in molecular classification, the pathogenesis of DLBCL, particularly of the BN2 subtype, remains poorly understood, which limits the advancement of tailored and more effective therapeutic strategies. BN2-DLBCL are characterized by alterations in BCL6 and NOTCH2, lack an AICDA mutational signature, and are presumed to arise outside germinal centers (GC). Among its defining alterations, truncating mutations in SPEN (SPENTRUNC) are significantly enriched, but the effects and clinical relevance of these alterations remain unexplored. Here, we found that SPENTRUNC likely represent loss-of-function (LOF) events, as they led to reduced SPEN protein levels (p=0.04). Clinically, SPENTRUNC mutations correlated with significantly worse overall survival (OS), especially in non-GCB DLBCL patients (HR: 1.82; p<0.0001). Co-occurring truncating mutations in NOTCH2 (NOTCH2TRUNC), which confer gain-of-function (GOF) effects, further worsened prognosis when in combination with SPENTRUNC (HR: 3.33; p<0.0001). Patients with dual SPENTRUNC/NOTCH2TRUNC (SN2) mutations were also older (p=0.03) and had poorer ECOG performance status (p=0.02), defining a high-risk subgroup urgently needing targeted therapies. To understand how SN2 mutations shape disease biology, we introduced B cell–specific SpenLOF and Notch2GOF mutations in mice. The SN2 genotype led to a cumulative expansion of autoimmune/aged B cells (AiBCs), a hyper-reactive inflammatory B cell subset implicated in autoimmunity and lymphomagenesis. Given the hypothesized extra-follicular origin of BN2-DLBCL, we tested whether AiBCs could arise in SN2 mice lacking Bcl6, which is essential for GC formation. Indeed, AiBC expansion occurred independently of GC formation, as SN2;Bcl6–/– and SN2 mice showed comparable AiBC levels, supporting their extra-follicular derivation. To further evaluate their malignant potential, we assessed clonality and proliferation in SN2 AiBCs versus their wild-type (WT) counterparts. SN2 AiBCs exhibited significantly higher clonality and proliferation (p<0.05). Notably, female SN2 AiBCs showed even greater proliferation (KI67+) than male SN2 AiBCs (p<0.0001), a difference not observed in WT mice. This disproportionate fitness of female SN2 cells translated to a competitive advantage, as shown by bone marrow chimera assays (p=0.04), regardless of the hormonal sex status of the recipient animal. Accordingly, female SN2 mice had significantly reduced survival due to lymphoma development than their male counterparts (OS HR: 13.4; p=0.001), a trend mirrored in human SN2-DLBCL patients (OS HR: 4.14; p=0.07). This sex-bias is of particular interest, as SPEN is known to be essential in X-chromosomal inactivation (XCI), a process happening in females to equilibrate X chromosomal gene dosage to male cells. Although XIST RNA-FISH did not reveal changes in XCI (p=0.2), SN2 lymphomas showed significant hypomethylation of the X chromosome compared to WT B cells and N2 lymphomas (p=5.9e-4). Autosomal regions, in contrast, were hypermethylated (p<2.2e-18), suggesting X-chromosome–specific dysregulation due to SPEN loss. Among X-linked genes, TLR7, a known AiBC driver, emerged as a candidate mediator. Indeed, female SN2 lymphomas expressed higher TLR7 levels than males (p=0.05). To test whether the TLR7 pathway confers an exploitable therapeutic vulnerability, we treated SN2 lymphoma cells with AZ1495, an IRAK1/4 inhibitor acting downstream of TLR7, and found that only female cells showed in vitro and in vivo sensitivity (p<0.05). Efficacy was further confirmed using a female human SN2-DLBCL PDX model (p=0.01), supporting the translational potential of targeting this axis. In summary, SPENTRUNC defines a poor-prognosis marker in DLBCL, and cooperates with NOTCH2TRUNC to drive aggressive, extra-follicular lymphomas via expansion of pathogenic AiBCs. We identify a novel, sex-biased pathogenic mechanism involving X-chromosomal dysregulation and TLR7 overexpression, offering a rationale for precision therapy in BN2-DLBCL.

  PublisherOA PDFDOI

• Table S6 from The FBXO45–GEF-H1 Axis Controls Germinal Center Formation and B-cell Lymphomagenesis

  2025-04-02

  preprintOpen accessSenior author

  <p>Supplementary Table S6, Details of the FISH probes used to identify copy number variations (CNV) affecting FBXO45 and ARHGEF2 in clinical samples.</p>

  PublisherDOI

• Palmitoylation by ZDHHC family members regulate B-cell lymphoma growth

  International Journal of Biological Macromolecules · 2025-07-15 · 2 citations

  articleOpen access

  The ZDHHC palmitoyl transferase family consists of 24 members, of which several have been linked to the development of cancer. We previously showed that inhibition of ZDHHC11 decreased growth of several B-cell lymphoma subtypes. In this study, we evaluated the effect of protein palmitoylation on the proteome in general and investigated expression and function of ZDHHC family members in a panel of Burkitt, Hodgkin and diffuse large B-cell lymphoma cell lines. Proteomic analysis of Burkitt lymphoma cells treated with the general palmitoylation inhibitor 2-bromopalmitate (2-BP) revealed 1089 differentially expressed proteins of which 124 were involved in cell cycle and apoptosis related gene ontologies. In line with this, 2-BP treatment resulted in an increased percentage of apoptotic cells in all three lymphoma subtypes. To allow a further selection of the most relevant family members of ZDHHC palmitoyl transferases, we studied expression patterns and assessed the dependency. The combined analyses revealed potential roles for ZDHHC11 and ZDHHC18 in the observed phenotype. Knockdown of ZDHHC18 in four Burkitt lymphoma cell lines revealed a decreased cell viability. This is the first study showing a critical role for palmitoylation in controlling growth of B-cell lymphoma. Moreover, we provide evidence that next to the previously identified ZDHHC11, ZDHHC18 is also crucial for B-cell lymphoma growth expanding the potential functional role for ZDHHC family members in lymphomagenesis.

  PublisherDOI

• Racial disparities in mycosis fungoides - from self-reported race to genetic ancestry analysis

  Blood · 2025-11-03

  articleOpen access

  Abstract Introduction: Racial disparities in mycosis fungoides (MF) and Sezary syndrome (SS) are well-documented, with self-identified Black patients being diagnosed younger, with more advanced disease, and worse survival. (Su C et al. J Am Acad Dermatol. 2017; Wilson LD et al. Clin Lymphoma Myeloma Leuk. 2012). Our previous work showed that these disparities persist after adjusting for socioeconomic factors (Gandham AR et al. Clin Lymphoma Myeloma Leuk. 2024) suggesting genetic ancestry may contribute. We compared clinical characteristics and outcome of MF/SS patients stratified by self-reported race versus genetic ancestry. Methods: Patients with confirmed MF/SS were consented for genetic profiling via Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT). Genetic ancestry was inferred using ADMIXTURE and single nucleotide polymorphisms (SNPs) captured by MSK-IMPACT (Arora K et al. Cancer discovery. 2022). Patients with ancestral fraction of >0.8 for any single population were assigned that population label; otherwise, they were considered admixed. Results: Genetic ancestry analysis of 161 MF/SS patients (104 self-reported White race, 30 Black, 7 Asian, 20 Other/Unknown) identified 74 as European (EUR), 21 Ashkenazi Jewish (ASJ), 23 African (AFR), 5 East/South Asian, 1 Native American and 37 as admixed. AFR patients were diagnosed 10 years younger than EUR/ASJ (p=0.01) and were less likely to present with stage IA disease compared to EUR/ASJ patients (0% vs 23.2%, p=0.01). Trends towards higher female dominance (52% vs. 35%, p=0.1), higher disease-related mortality (22% vs 12%, p=0.2) and worse progression-free survival (PFS, p=0.11) were observed in AFR patients. ASJ patients showed a trend toward improved PFS compared to EUR patients (p=0.08). Conclusions: Our novel ancestry-based stratification of MF/SS patients confirms disparities seen in self-reported race groups, supporting the need to further investigate specific genetic and non-genetic contributors to disparities in MF/SS patients.

  PublisherOA PDFDOI

• NPM::ALK TRANSCRIPT LEVELS AND ANTI-ALK AUTOANTIBODY TITERS AS BIOMARKERS FOR OUTCOME IN PEDIATRIC ALK+ ANAPLASTIC LARGE CELL LYMPHOMA TREATED WITH BRENTUXIMAB VEDOTIN OR CRIZOTINIB IN COMBINATION WITH CHEMOTHERAPY: COG ANHL12P1

  Leukemia Research · 2025-09-01

  article
  PublisherDOI

Frequent coauthors

• Megan S. Lim

  Memorial Sloan Kettering Cancer Center

  450 shared

• David K. Crockett

  97 shared

• Delphine C.M. Rolland

  Institut Pluridisciplinaire Hubert Curien

  84 shared

• Zhaosheng Lin

  82 shared

• Sherrie L. Perkins

  University of Utah

  77 shared

• L. Jeffrey Medeiros

  The University of Texas MD Anderson Cancer Center

  73 shared

• Noah A. Brown

  University of Michigan–Ann Arbor

  69 shared

• Nathanael G. Bailey

  University of Pittsburgh

  59 shared

Awards & honors

• Harold Amos Medical Faculty Development Award (year not spec…
• Byron B. Oberst Award from the American Academy of Pediatric…
• Elected into the American College of Medical Informatics (20…
• Elected into The Academic Pediatric Society (2010)
• Elected into the National Academy of Medicine (Institute of…