About

Iannis Aifantis, PhD, is the Hermann M. Biggs Professor of Pathology and Chair of the Department of Pathology at NYU Grossman School of Medicine. His laboratory focuses on the molecular mechanisms of differentiation and transformation of hematopoietic stem cells and progenitors, with specific emphasis on lymphoid (T-ALL, B-ALL) and myeloid (AML, CML, CMML) leukemia initiation and progression. His research has identified and studied novel oncogenes, tumor suppressors, and downstream oncogenic signaling pathways, which have been used to design molecularly targeted therapeutic protocols to inhibit or affect the maintenance of these malignancies. Additionally, his work explores mechanisms of hematopoietic stem cell differentiation and self-renewal through genomic and genetic approaches, including the impact of DNA methylation, long non-coding RNAs, RNA-binding proteins, 3D chromosomal architecture, stress responses, and tumor microenvironment mapping in leukemia.

Research topics

• Biology
• Medicine
• Cancer research
• Genetics
• Immunology
• Internal medicine
• Oncology
• Molecular biology
• Cell biology

Selected publications

• 3D chromosome remodeling in B-cell development and acute lymphoblastic leukemia

  Blood Cancer Discovery · 2026-04-14

  articleOpen accessSenior author

  The identification of molecular subgroups of pediatric B-cell acute lymphocytic leukemia (B-ALL) has proven to be a powerful tool in understanding disease pathogenesis and treatment stratification. Studies have suggested aberrant transcription factor function and epigenetic regulation can explain differences between B-ALL subtypes, however, the impact of 3D genome re-organization remains unclear. Here we used in situ Hi-C and RNA-seq to profile the chromatin architectural landscape in healthy B-cell progenitors and B-ALL patient samples harboring prognostically relevant structural variations, including ETV6::RUNX1, KMT2A::AFF1, and BCR::ABL. We showed that B-ALLs undergo subtype-specific changes that, in part, reflect the differentiation stage of the disease, and that they acquire aberrant chromatin configurations that allow expression of oncogenic drivers. One such driver, ERG, displayed increased interactivity and expression in ETV6::RUNX1 B-ALL, and evidence suggests it plays a role in regulating survival and differentiation. Overall, these results underscore the essential role of 3D nuclear organization in acute leukemia.

  PublisherOA PDFDOI

• (Sub)Clonal Wars: Interferon Interference Yields the Upper Hand

  Blood Cancer Discovery · 2025-12-12

  articleSenior author

  Intratumoral heterogeneity and subclonal diversity, characterized by the coexistence of genetically and functionally distinct leukemic cell populations within a single patient, have long been recognized as major contributors to chemotherapy resistance and disease relapse in acute myeloid leukemia. In this issue of Blood Cancer Discovery, Karigane and colleagues delve into the mechanisms that underlie the interactions between distinct leukemic subpopulations and identify Interferon signaling as a critical regulator that determines clonal dominance and expansion. See related article by Karigane et al., p. 68.

  PublisherDOI

• Publisher Correction: The pre-T cell receptor as a tumor immunotherapy target in T cell leukemia

  Nature Immunology · 2025-09-16

  erratumOpen accessSenior author
  PublisherOA PDFDOI

• Supplementary Table S1 from Mitophagy Promotes Resistance to BH3 Mimetics in Acute Myeloid Leukemia

  2025-12-11

  articleOpen accessSenior author

  <p>Supplementary Table 1 shows the results of our CRISPRi screens.</p>

  PublisherDOI

• Supplementary Figures 1-7 from Mitophagy Promotes Resistance to BH3 Mimetics in Acute Myeloid Leukemia

  2025-12-11

  articleOpen accessSenior author

  <p>Supplemental Figure S1 shows the integration of CRISPR/Cas9 loss-of-function screens to identify dependencies and liabilities in BH3-mimetics treatments. Supplemental Figure S2 demonstrates that increased mitochondria-ER interactions contribute to BH3-mimetics resistance. Supplemental Figure S3 shows that mitophagy affects the responsiveness of AML cells to BH3-mimetics. Supplemental Figure S4 reveals that enhanced autophagic clearance of mitochondria as a mechanism of resistance to BH3-mimetics in AML. Supplemental Figure S5 exhibits the synergism between BH3-mimetics and macroautophagy inhibition in human AML. Supplemental Figure S6 shows that deletion of MFN2 or MARCH5 sensitizes AML cells to BH3-mimetics. Supplemental Figure S7 displays that targeting of MFN2 or MARCH5 impairs the process of mitophagy.</p>

  PublisherDOI

• Epigenetic reactivation of a tumor suppressor program in AML.

  Blood · 2025-11-03

  articleOpen access

  Abstract Inactivation of tumor suppressor genes (TSGs) impart a cellular fitness in cancers, including acute myeloid leukemia (AML). The silencing of TSGs without direct mutations presents challenges in cancer therapy but also presents a therapeutic opportunity to restore their function. In this study, we identified the transcriptional repressor ZBTB7A as a TSG that is downregulated in AML and associated with poor survival outcomes. Loss of ZBTB7A amplifies TNF signaling, driving a dysfunctional inflammatory state that accelerates leukemia progression. Mechanistically, the mRNA decay factor ZFP36L2 binds to the 3' untranslated region (3'UTR) of ZBTB7A, promoting its transcript degradation. To uncover therapeutic strategies, we developed a CRISPR-based screening approach coupled with in situ FISH-Flow, pinpointing KDM4 as a vulnerability to restore ZBTB7A function. Pharmacologic inhibition of KDM4 enhanced ZBTB7A expression, promoted terminal differentiation of leukemic cells, and demonstrated broad anti-leukemic activity across AML subtypes while preserving normal hematopoiesis. These findings reveal critical regulatory mechanisms of ZBTB7A and support epigenetic therapy as a promising strategy to reactivate its tumor suppressor function in hematologic cancers.

  PublisherOA PDFDOI

• Figure S4 from Uncovering Novel lncRNAs Linked to Melanoma Growth and Migration with CRISPR Inhibition Screening

  2025-07-09

  preprintOpen access

  <p>Apoptosis and lncRNA OE transmigration assays</p>

  PublisherOA PDFDOI

• Supplementary Table S5 from Mitophagy Promotes Resistance to BH3 Mimetics in Acute Myeloid Leukemia

  2025-12-11

  articleOpen accessSenior author

  <p>Supplementary Table S5 shows sgRNA, primers, shRNA sequences used in this study.</p>

  PublisherDOI

• Non-coding variants in UBA1 lead to vexas

  Blood · 2025-11-03

  articleOpen access

  Abstract Introduction: Somatic mutations in UBA1, encoding an E1 ubiquitin activating enzyme, have recently been linked to an adult-onset, severe inflammation syndrome called VEXAS (Vacuoles, E1-enzyme, X-linked, Autoinflammatory, Somatic). VEXAS is characterized by systemic inflammation and hematologic abnormalities. While the majority of identified mutations in UBA1 are located in exonic regions, the role of non-coding and intronic mutations in the pathogenesis of VEXAS remains largely unexplored. In this study, we investigated the potential contribution of intronic mutations to VEXAS pathogenesis. Methods: To investigate mutations affecting UBA1 outside the region typically covered in targeted panels (exon 3), whole exome (WES) and genome sequencing (WGS) was performed on peripheral blood of patients with VEXAS-associated clinical presentation previously negative for UBA1 mutations per clinical testing. 265 patients were profiled by WES (~100X) and 36 patients were profiled by WGS (~55X). Clinical history was reviewed for these patients for VEXAS-associated presentation including a combination of hematologic and rheumatologic disease in adults. Participants with known pathogenic or likely pathogenic (P/LP) variants in UBA1 or other genetic causes of systemic autoinflammatory disease were excluded. UBA1 transcript and protein expression were assessed by PCR and western blot, respectively, in one case where peripheral blood mononuclear cells were available. Results: We identified 7 patients with VEXAS-like presentation with intronic single nucleotide variants or deletions. Five patients had a recurrent point mutation (median VAF: 0.78; range: 0.38-0.97). 5 patients had been diagnosed with MDS, and bone marrow biopsy revealed vacuolated progenitor cells in 3 patients. The most frequent clinical manifestations included skin rash (n=6), joint pain (n=4), vasculitis (n=4), and chondritis (n=2). One patient had been diagnosed with acute myeloid leukemia with myelodysplasia related changes, with co-mutations in IDH1 and SRSF2. Two additional patients had mutations in ASXL1 of which one also had a ZRSR2 mutation. No co-occurring myeloid driver gene mutations were found in the other cases. Noncoding mutations, similar to canonical UBA1 disease causing mutations, were shown to be lineage restricted to myeloid cells. To assess the functional impact of mutations, CD14+ monocytes were isolated from the peripheral blood. Compared to the CD14- fraction, the CD14+ fraction revealed a decrease in the UBA1 transcript as well as UBA1 protein level. One patient demonstrated loss of novel UBA1 mutation after hypomethylating agent treatment, and allogeneic transplant, placing the patient in remission.Conclusions:Our findings of intronic and non-coding UBA1 mutations in patients with VEXAS-associated clinical presentation suggests these variants may affect the regulation of UBA1 transcription, representing a potential new mechanism of pathogenesis. Further functional studies are underway to understand how these variants contribute to impaired UBA1 activity and VEXAS disease pathogenesis. Collectively, our results advocate for a broader approach in genetic testing for UBA1 mutations and pave the way for improved diagnostic and therapeutic strategies for VEXAS syndrome.

  PublisherOA PDFDOI

• Figure 4 from Uncovering Novel lncRNAs Linked to Melanoma Growth and Migration with CRISPR Inhibition Screening

  2025-07-09

  preprintOpen access

  <p>XLOC_030781 CRISPRi knockdown and RNA-seq transcriptomic expression analysis in 501mel-dCas9-KRAB. <b>A,</b> Principal component analysis (PCA) of sgXLOC_030781 CRISPRi at days 3 and 5 after infection vs. day 0 negative control (<i>n</i> = 2). <b>B,</b> Volcano plot of significantly differentially expressed genes (red) upon sgXLOC_030781 knockdown at day 3; <i>P</i> value cutoff = 0.05 and log<sub>2</sub> fc = 1. <b>C,</b> GO enrichment analysis of up- and downregulated gene sets upon sgXLOC_030781 knockdown at day 3. <b>D,</b> GSEA enrichment analysis of each top example of upregulated (ER to Golgi vesicle transport, left) and downregulated genes (DNA replication–dependent nucleosome assembly, right). <b>E,</b> Upstream TF analysis of up- and downregulated genes using ChEA upon sgXLOC_030781 knockdown at day 3.</p>

  PublisherDOI

Recent grants

• Mapping cancer micro-environments for acute leukemia

  NIH · $2.3M · 2016–2021

• Targeting an RNA Binding Protein Network in Acute Myeloid Leukemia

  NIH · $2.7M · 2020–2025

• NIH Grant R21CA141399

  NIH · $399k · 2012

• NIH Grant R01CA149655

  NIH · $2.0M · 2016

• Long non-coding RNAs in hematopoiesis and blood malignancy

  NIH · $2.3M · 2015–2020

Frequent coauthors

• Aristotelis Tsirigos

  NYU Langone’s Laura and Isaac Perlmutter Cancer Center

  165 shared

• Harald von Boehmer

  Harvard University

  115 shared

• Panagiotis Ntziachristos

  Ghent University Hospital

  104 shared

• Camille Lobry

  Inserm

  72 shared

• Thomas Trimarchi

  New York University

  62 shared

• Xufeng Chen

  New York University

  55 shared

• María Guillamot

  51 shared

• Omar Abdel‐Wahab

  Memorial Sloan Kettering Cancer Center

  50 shared

Labs

• Health Tech Hub TeamPI