Dataset Information

Targeting Menin in T-Lineage Acute Lymphoblastic Leukemia

ABSTRACT: The efficacy of menin inhibition was evaluated in 14 primary T-ALL samples with diverse genetic backgrounds using ziftomenib. Sensitivity was not correlated with HOXA expression or KMT2A rearrangements, and in vivo treatment significantly reduced tumor burden in xenograft models without notable toxicity. Transcriptomic and proteomic analyses confirmed on-target activity, including downregulation of menin targets and activation of differentiation pathways. Phosphoproteomic profiling identified phospho-MEF2C (S222) as a key marker of sensitivity, regulated by CDK and MAPK signaling. Combination treatment with ziftomenib and CDK1/2 or ERK1/2 inhibitors showed synergistic effects, suggesting a mechanistic link between menin inhibition and p-MEF2C–driven T-ALL vulnerability.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Leukocyte, Blood

DISEASE(S): Acute Leukemia

SUBMITTER: Diren Arda Karaoglu

LAB HEAD: Caner Saygin

PROVIDER: PXD065185 | Pride | 2026-03-05

REPOSITORIES: Pride

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Targeting menin in T-lineage acute lymphoblastic leukemia.

Shimamoto Kathryn K Karaoglu Diren Arda DA Arnold Olivia O Dhar Arjun A Chan Zachary Z Giordano Giorgia G Cheng Jason X JX Youshanlouei Hamed R HR Patel Anand A AA DuVall Adam S AS Drazer Michael W MW Kessler Linda L Burrows Francis F Odenike Olatoyosi O Thirman Michael J MJ Stock Wendy W Saygin Caner C

Molecular cancer therapeutics 20260304

T-lineage acute lymphoblastic leukemia (T-ALL) lacks effective targeted therapies, with poor outcomes in relapsed/refractory disease. HOXA-high T-ALL is biologically aggressive and often resistant to standard therapy. Menin inhibitors, recently approved for KMT2A-rearranged leukemias, may be effective in T-ALL, but biomarkers of response remain undefined. This study aims to evaluate the efficacy of menin inhibition in T-ALL and identify molecular predictors of sensitivity. We tested menin inhibi ...[more]

PMID: 41778833

			Action	DRS
	T-ALL3_treated_r1.raw	Raw
	T-ALL3_treated_r2.raw	Raw
	T-ALL3_untreated_r1.raw	Raw
	T-ALL3_untreated_r2.raw	Raw
	T-ALL8_treated_r1.raw	Raw

Dataset Information

Targeting Menin in T-Lineage Acute Lymphoblastic Leukemia

Dataset's files

Publications

Targeting menin in T-lineage acute lymphoblastic leukemia.

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