Tuesday, July 1, 2025 7/1/2025

BCLW in lymphoma survival and resistance to targeted BCL2 family therapies

Award Number: R01CA236853
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2025

Group Awards By:

View Award Description

BCLW in lymphoma survival and resistance to targeted BCL2 family therapies - Summary A prerequisite for tumor development is acquiring resistance to apoptosis. This can be accomplished through multiple mechanisms, but a frequent alteration in human cancers that protects from apoptosis is the overexpression of one or more of the anti-apoptotic BCL2 family members. BCL2 itself is frequently overexpressed in multiple types of B cell lymphomas and many other lymphoid and non-lymphoid malignancies. Because of the perceived reliance of cancer cells on BCL2 for survival, a targeted specific BCL2 inhibitor was developed, ABT-199 (venetoclax). Although, venetoclax has been FDA approved for the treatment of specific leukemias, clinical trials with venetoclax have not been successful for B cell lymphomas with high levels of BCL2, such as follicular lymphomas and diffuse large B cell lymphomas (DLBCL) that have translocated or amplified BCL2. The results indicate these lymphomas do not require BCL2 for their continued survival, revealing a significant gap in knowledge of what lymphomas use to protect themselves from apoptosis. Recently, we made the unexpected discovery that BCLW, an unexplored anti-apoptotic BCL2 family member that was only thought to be important in spermatogenesis, was overexpressed in six different types of B cell lymphomas, including follicular lymphoma and DLBCL. We determined patients with DLBCL containing higher levels of BCLW had reduced survival, and BCLW was more highly expressed than BCL2 in higher grade follicular lymphoma. We also showed BCLW was necessary for the survival of Burkitt lymphoma cells, and increased levels of BCLW provided resistance to Burkitt lymphoma cells to an inhibitor that targets three anti-apoptotic BCL2 family members. Therefore, we hypothesize BCLW overexpression is necessary for the survival of multiple types of B cell lymphomas and confers resistance to lymphoma cells to venetoclax and other BCL2 family inhibitors. We propose two Aims to test this hypothesis. In Aim 1, we propose to evaluate the requirements of BCLW in multiple different B cell lymphomas in relationship to other BCL2 family members and mechanisms for its overexpression. In Aim 2, we propose to determine the contribution of BCLW to resistance to inhibitors of anti-apoptotic BCL2 family members and ways to overcome this resistance. Completion of these Aims will significantly increase knowledge into the BCL2 family of proteins and the contribution of BCLW to B cell lymphomas and resistance to targeted inhibitors of BCL2 family members. Results are also likely to lead to improved lymphoma clinical trials, diagnostics, prognostics, and therapeutic interventions with knowledge based treatment combinations.


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: 2025 ( Subtotal = $364,182 )
2025	2025	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Cancer Biology Research	000	6	11/25/2024	NON-COMPETING CONTINUATION	$327,764
2025	2025	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Cancer Biology Research	001	6	6/24/2025	NON-COMPETING CONTINUATION	$36,418
														Subtotal = $364,182

Issue Date FY: 2024 ( Subtotal = $355,240 )
2024	2024	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Cancer Biology Research	001	5	4/23/2024	NON-COMPETING CONTINUATION	$18,697
2024	2024	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Cancer Biology Research	000	5	11/29/2023	NON-COMPETING CONTINUATION	$336,543
														Subtotal = $355,240

Issue Date FY: 2023 ( Subtotal = $112,885 )
2023	2023	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Cancer Biology Research	000	4	2/1/2023	NON-COMPETING CONTINUATION	$112,885
														Subtotal = $112,885

Issue Date FY: 2022 ( Subtotal = $421,205 )
2022	2022	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Cancer Biology Research	001	3	6/22/2022	NON-COMPETING CONTINUATION	$34,384
2022	2022	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Cancer Biology Research	000	3	11/30/2021	NON-COMPETING CONTINUATION	$386,821
														Subtotal = $421,205

Issue Date FY: 2021 ( Subtotal = $429,800 )
2021	2021	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Cancer Biology Research	000	2	11/19/2020	NON-COMPETING CONTINUATION	$408,311
2021	2021	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Cancer Biology Research	001	2	1/22/2021	NON-COMPETING CONTINUATION	$21,489
														Subtotal = $429,800

Issue Date FY: 2020 ( Subtotal = $429,800 )
2020	2020	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Cancer Biology Research	001	1	1/23/2020	NEW	$10,357
2020	2020	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Cancer Biology Research	000	1	11/14/2019	NEW	$419,443
														Subtotal = $429,800

Grand Total All Awards = $2,113,112

Top

All Categories

About

Search

Reports

Data Submission

Award Information

BCLW in lymphoma survival and resistance to targeted BCL2 family therapies

Award Number: R01CA236853

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer