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Identifying the mechanisms of leukemia progression

Award Number: R35CA253096
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/22/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Identifying the mechanisms of leukemia progression - PROJECT SUMMARY Since 2002 when my laboratory discovered GATA1 mutations in all cases acute megakaryocytic leukemia in children with Down syndrome, I have been at the forefront of defining the specific genetic events that promote leukemia. I have extensively studied the role of GATA1 in normal and malignant hematopoiesis and gained many insights into the contributions of several chromosome 21 genes, including DYRK1A, ERG and CHAF1B, in leukemia. My laboratory is also well established in the field of the myeloproliferative neoplasms (MPNs), especially in the role of megakaryocytes in the pathogenesis of myelofibrosis and the development of new therapies for this disease. In this R35 application, I propose to focus my laboratory over the next 7 years (and beyond) on understanding the mechanisms of leukemia progression from clonal hematopoietic disorders. Specifically, we will identify and compare the ways that pediatric and adult disorders progress to acute myeloid leukemia. We will leverage large scale CRISPR/Cas9 screening, animal models and primary patient samples to deeply characterize the mechanisms of transformation and focus on answering three questions: 1) What are the similar and disparate events that promote malignant progression of pediatric versus adult blood disorders? 2) How does dysregulation of pathways downstream of identified tumor suppressor genes promote malignant progression? 3) Which investigational or approved therapies can prevent progression or treat the tumors? The answers to these questions will increase our basic understanding of cancer, reveal new therapeutic targets and possibly shed light on chemoprevention strategies.


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 = $1,077,000 )
2025	2025	ST JUDE CHILDREN'S RESEARCH HOSPITAL INC	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Cancer Biology Research	000	5	8/22/2025	NON-COMPETING CONTINUATION	$1,077,000
														Subtotal = $1,077,000

Issue Date FY: 2024 ( Subtotal = $767,359 )
2024	2024	ST JUDE CHILDREN'S RESEARCH HOSPITAL INC	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Cancer Biology Research	000	4	8/19/2024	NON-COMPETING CONTINUATION	$767,359
														Subtotal = $767,359

Issue Date FY: 2023 ( Subtotal = $1,055,460 )
2023	2023	ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Cancer Biology Research	000	3	9/5/2023	NON-COMPETING CONTINUATION	$1,055,460
														Subtotal = $1,055,460

Issue Date FY: 2022 ( Subtotal = $1,055,460 )
2022	2022	ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Cancer Biology Research	000	2	8/5/2022	NON-COMPETING CONTINUATION	$1,055,460
														Subtotal = $1,055,460

Issue Date FY: 2021 ( Subtotal = $1,077,000 )
2021	2021	ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.	262 DANNY THOMAS PL	MEMPHIS	TN	38105	SHELBY	USA	Cancer Biology Research	000	1	9/22/2021	NEW	$1,077,000
														Subtotal = $1,077,000

Grand Total All Awards = $5,032,279

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Identifying the mechanisms of leukemia progression

Award Number: R35CA253096

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/22/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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