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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 22/07/2026

These data will be important in future clinical development of BTK degraders and considering new modalities to target. Thank you to @bloodcancerunited.bsky.social, @ascocancer.bsky.social, @mskcancercenter.bsky.social, NCI, and the CLL Society for their support.

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 22/07/2026

Importantly, this mutation confers a profound fitness disadvantage in the absence of selection pressure from BTK-targeting agents & co-treatment with BCL2 inhibitors mitigates the expansion of BTK A428D in the setting of BTK degrader treatment:

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 22/07/2026

We functionally, biochemically, & structurally characterize a very unique mutation in BTK (BTK A428D) which is rarely seen in CLL patients but selected for under the specific pressure of BTK degraders. BTKA428D confers cross-resistance to all FDA-approved BTK inhibitors and degraders in development:

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 22/07/2026

Excited to announce a new paper out today in Cancer Discovery @aacrjournals.bsky.social on clinical mechanisms of resistance to BTK degraders. Led by @quinnsievers.bsky.social and part of our ongoing collaboration with Meghan Thompson, Nurix Therapeutics & Justin Taylor (U. Miami):

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 12/05/2026

This study opens many new research directions for our group and will hopefully be a useful resource for the field. Thanks to Neil Hirsch Foundation, @break_cancer, @ASH_hematology, @BloodCancerUtd, @nih_nhlbi, @theNCI, @TheVFoundation, & Edward P. Evans MDS Foundation.

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 12/05/2026

We identify a mechanism for clonal expansion of MDS through local immunosuppressive effects of MDS mutant cells through secretion of TGFb, as well as cell intrinsic effects as mutant cells themselves have dampened recognition of TGFb (gorgeous art by @DrawImpacts):

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 12/05/2026

Through the use of custom probes we track clonal populations of T cells over time and space in the marrow and identify SF3B1 mutant cells in situ. These studies enabled differential gene expression and niche analyses of clonal cells in tissue:

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 12/05/2026

Now across a cohort of 41 patients with MDS and 15 bone marrow biopsies from age-matched normal individuals we capture 5.7M cells and identified new cellular niches characteristic of human MDS & lymphoid aggregates unique to MDS marrow:

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 12/05/2026

Led by Susan DeWolf, Rob Stanley, Beatrice Zhang, Kimon Argyropoulos, Stephen Martis & collab with Ben Greenbaum. Prior studies have identified important roles for the microenvironment in MDS but transcriptomic studies of the native marrow in patients with MDS have been limited to date:

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 12/05/2026

Excited to present the first pre-print from our group, an investigation the human bone marrow microenvironments in patients with myelodysplastic syndromes (MDS) and normal age-matched subjects using Xenium genotype-informed spatial transcriptomics: www.biorxiv.org/content/10.6...

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 01/05/2026

We are now excited to move this forward and are working towards an IND application. Thank you to the Neil Hirsch Foundation, @bloodcancerunited.bsky.social , @ash.hematology.org, Edward P. Evans MDS Foundation, NCI, and NHLBI for support.

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 01/05/2026

Armoring CAR-T cells with IL-18 led to antigen gain on AML, durable remission, and protection from AML rechallenge. These data thereby identify a CAR-T cell platform which addresses prior limitations in tumor-selectivity and safety for patients with acute leukemias.

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 01/05/2026

Anti-U5 snRNP200 CAR-T cells were effective in human and syngeneic models of AML as well as B-cell acute lymphoblastic leukemia (B-ALL), a setting where surface U5 snRNP200 is also present.

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 01/05/2026

We used autoantibodies responsible for graft-versus-leukemia to create CAR-T cells. We generated CAR-T cells against one such antigen - U5 snRNP200, an RNA helicase localized to the surface of AML but not normal hematopoietic precursors. Described here:

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 01/05/2026

Collaboration with @DaniyanMd and led by Takeshi Fujino & Jen Lewis. Developing CAR T cells for AML has been challenging due to a lack of known AML-associated antigens that spare normal hematopoietic precursor cells.

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 01/05/2026

Excited to announce a new paper out now in Cancer Discovery @aacrjournals.bsky.social on a unique CAR T cell platform that eliminates AML and B-ALL without harming vital endogenous immune cells or other normal human tissues: pubmed.ncbi.nlm.nih.gov/42059863/

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 11/03/2026

We are now excited to move this forward in prospective trials of patients with CDK4/6 independent cancers & high leukemia risk. Thank you to the Neil Hirsch Foundation, @break-cancer.bsky.social , @ash.hematology.org , LLS, Edward P. Evans MDS Foundation, NCI, NHLBI, and V Foundation for support.

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 11/03/2026

Similarly, in a mouse model of TP53 mutant clonal hematopoiesis, we found that contemporaneous administration of a CDK4/6 inhibitor with platinum chemotherapy mitigated p53 mutant cell expansion with chemotherapy:

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 11/03/2026

The development of therapy-related myeloid neoplasms is one of the most dangerous complications of cancer-directed therapy. Here we identify across 4 randomized trials that short-term CDK4/6 inhibition mitigates clonal expansion of TP53 mutant hematopoietic cells during cytotoxic chemotherapy.

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 06/03/2026

Thanks so much for having me @uwmadisonrna.bsky.social , Aaron, and the Hoskins lab! I had a great time!

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 23/10/2025

Our phase II trial of Ulixertinib in adults with histiocytosis is open and enrolling so please reach out with any referrals: clinicaltrials.gov/study/NCT064...

clinicaltrials.gov

ClinicalTrials.gov

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 23/10/2025

Importantly both mice and patients with class 3 MEK mutations respond to ERK inhibition with Ulixertinib. Through FDA compassionate use and help of @BioMedValley, we treated 5 MEK1 E102_I103del mutant patients with Ulixertinib and saw partial or complete responses:

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 23/10/2025

We then created a conditional knockin mouse model of the most common MEK mutation – MEK1 E102_I103del and fund that these mice develop a high penetrance histiocytosis affecting the skin and hematopoietic organs:

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 23/10/2025

Now across an international cohort of 498 patients we identify that RAF-independent MEK mutations (which are common amongst histiocytosis patients) are associated with progression to MEK inhibition:

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 23/10/2025

Led by Eli Diamond and former Abdel-Wahab lab member (now RutgersCancer) Benjamin Durham + Takeshi Fujino. Prior work by our group led to FDA-approval of vemurafenib for BRAFV600E mutant histiocytosis followed by Cobimetinib for BRAF WT: www.nature.com/articles/s41...

nature.com

Efficacy of MEK inhibition in patients with histiocytic neoplasms - Nature

A proof-of-concept clinical trial of patients with histiocytoses with MAPK-pathway mutations showed durable responses to treatment with the MEK1 and MEK2 inhibitor cobimetinib, which indicates that hi...

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 23/10/2025

Excited to announce a new publication from our @mskcancercenter.bsky.social Histiocytosis group identifying a predictor for impaired response to MEK inhibition in histiocytosis patients and potential for ERK inhibition. Out today in @Cancer_Cell. www.sciencedirect.com/science/arti...

sciencedirect.com

RAF-independent MEK mutations drive refractory histiocytic neoplasms but respond to ERK inhibition

Histiocytic neoplasms are clonal disorders of the monocyte/macrophage lineage defined by mutations activating mitogen-activated protein kinase (MAPK) …

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 12/08/2025

It turns out that ARHGAP45 also encodes the first identified minor histocompatibility antigen (HA-1) and we present a new cell therapeutic approach to target HA-1 and upregulate ARHGAP45 derived epitopes. Thanks to @LLSusa, @theNCI, @MSKCancerCenter for their support.

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 12/08/2025

Excited to announce a new paper in ‪@aacrjournals.bsky.social‬ with Junwei Shi and Tony Daniyan. We perform screens of GAPs and GEFs in AML and discover a hematopoietic-specific GAP (ARHGAP45) required in a variety of hematologic malignancies: aacrjournals.org/cancerdiscov...

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Reposted by Abdel-Wahab Lab, MSKCC

Elizabeth McKenna @elizsmckenna.bsky.social · 12/08/2025

Now online in Cancer Discovery @aacrjournals.bsky.social: Systematic Evaluation of GAPs & GEFs Identifies a Targetable Dependency for Hematopoietic Malignancies - by Pu Zhang, Zhendong Cao, Anthony Daniyan, Omar Abdel-Wahab, Junwei Shi, et al. doi.org/10.1158/2159...

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 03/05/2025

Excited to announce our annual New York City Edward P. Evans MDS Centers Symposium across @mskcancercenter.bsky.socia & @columbiacancer.bsky.social. This year to be held at @mskcancercenter.bsky.socia. See this flyer below and register here: forms.fillout.com/t/1wX3dGmym4us

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 24/04/2025

Thanks @raflynn5.bsky.social ! congrats on the cell surface NPM1 paper this week as well.

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 23/04/2025

We are excited to develop this as a novel cell therapy for myeloid leukemia patients with mutations in splicing factors. Thank you to @break-cancer.bsky.social, ASH, LLS, Edward P. Evans MDS Foundation, NCI, NHLBI, and @parkerici.bsky.social for support.

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 23/04/2025

Importantly we were able to identify neoantigen-specific CD8 T cells in patients with active MDS and AML. However, these neoantigen specific T cells had clear evidence of dysfunction, likely explaining the initiation/maintenance of these malignancies.

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 23/04/2025

We now find that MDS and AML patients with mutations in the splicing machinery create endogenous mis-splicing derived immunogenic peptides which are shared across patients (“public”) and were used to isolate tumor-selective TCRs.

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 23/04/2025

In 2021 in collaboration with the Bradley lab we identified that pharmacologic modulation of splicing creates bona fide RNA mis-splicing derived neoantigens which can augment immune checkpoint blockade efficacy in syngeneic solid tumor models:

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 23/04/2025

Mutations in genes encoding RNA splicing factors occur in 50-80% of patients with myelodysplastic neoplasms and create stereotyped changes in RNA splicing consistent across patients.

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 23/04/2025

This is part of a long-standing collaboration with Rob Bradley’s lab ‪@fredhutch.bsky.social‬ and with amazing TCR discovery expertise from Chris Klebanoff’s lab @klebanofflab.bsky.social @mskcancercenter.bsky.social‬‬. Also incredible help from Jeff Molldrem @mdanderson.bsky.social‬‬‬‬‬

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 23/04/2025

Excited to announce a new paper out today in @cp-cell.bsky.social discovering RNA mis-splicing derived neoantigens & their cognate T cell receptors (TCRs) as well as characterization of endogenous neoantigen T cells in leukemia patients. authors.elsevier.com/sd/article/S...

authors.elsevier.com

ScienceDirect.com | Science, health and medical journals, full text articles and books.

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Abdel-Wahab Lab, MSKCC @oawlab.bsky.social · 09/12/2024

Thanks so much @mikemfernandez.bsky.social ! Congrats on all of your success at #ASH24 and your award!

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