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The role of TBL-1 in acute lymphoblastic leukemia

Award Number: R01CA305140
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2031

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The role of TBL-1 in acute lymphoblastic leukemia - PROJECT SUMMARY Pediatric B-cell and T-cell acute lymphoblastic leukemia (B-/T-ALL) remains difficult to cure after relapse, underscoring the need for new treatment strategies. Wnt/â-catenin signaling contributes to leukemia cell survival and drug resistance, yet effective Wnt-directed therapies for leukemia are lacking. TBL1, a nuclear adaptor that stabilizes â-catenin and promotes Wnt-dependent transcription, is linked to poor outcome in acute myeloid leukemia, but its role in B-/T-ALL is not defined. We hypothesize that TBL1 drives drug resistance in B-/T-ALL and that disrupting TBL1-â-catenin interactions is a new therapeutic strategy. We will define TBL1-mediated resistance mechanisms and determine (1) leukemia-intrinsic and (2) microenvironmental mechanisms of Tegavivint-induced chemosensitization, and (3) optimize Tegavivint in preclinical models. The proposed experiments require an intact immune system and a physiologically relevant tumor microenvironment. Since in vitro systems and computational models cannot fully replicate the complex interactions between leukemia cells, stromal components, and immune cells in vivo we will use well established murine models of leukemia.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $609,010 )
2026	2026	CHILDREN'S HOSPITAL LOS ANGELES	4650 W SUNSET BLVD	LOS ANGELES	CA	90027	LOS ANGELES	USA	Cancer Treatment Research	000	1	8/20/2026	NEW	$609,010
														Subtotal = $609,010

Grand Total All Awards = $609,010

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The role of TBL-1 in acute lymphoblastic leukemia

Award Number: R01CA305140

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2031

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