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The role of clonal hematopoiesis in the development and therapy of myeloid malignancies

Award Number: R35CA253125
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2020
PERIOD OF PERFORMANCE END DATE: 11/01/2024

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The role of clonal hematopoiesis in the development and therapy of myeloid malignancies - PROJECT SUMMARY Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-associated condition in which a clonal, somatic mutation that is associated with myeloid malignancies is detectable in the peripheral blood at a variant allele fraction of at least 2%. Commonly mutated genes include the DNMT3A, TET2, and ASXL1 genes, all of which are present in myeloid malignancies and are commonly acquired early in the genetic ontogeny of these cancers. Individuals with CHIP do not have a hematologic malignancy or altered blood counts, but have a 10 to 50-fold increased risk of progression to hematologic malignancy, depending on the size of the clone and the specific somatic mutation. We propose to examine the biology of individual mutations and to understand cell-autonomous and cell non-autonomous mechanisms of clonal dominance. We will examine progression from CHIP to malignancy and the ongoing addiction of the malignant cells to the truncal mutations, thereby validating these mutations as therapeutic targets. We will integrate these biological studies with large-scale genetic studies to examine the risk of malignant transformation and clinical consequences of specific mutations. Finally, in the context of solid tumors, we will examine how CHIP generates tumor- infiltrating macrophages with aberrant function, and how these somatically mutated macrophages influence solid tumor biology, immune response, and response to immunotherapy.


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 = -$604,154 )
2025	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Biology Research	001	5	3/26/2025	NON-COMPETING CONTINUATION	-$604,154
2025	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Biology Research	000	5	1/28/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = -$604,154

Issue Date FY: 2024 ( Subtotal = $954,038 )
2024	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Biology Research	000	5	7/30/2024	NON-COMPETING CONTINUATION	$954,038
														Subtotal = $954,038

Issue Date FY: 2023 ( Subtotal = $984,165 )
2023	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Biology Research	000	4	7/24/2023	NON-COMPETING CONTINUATION	$984,165
														Subtotal = $984,165

Issue Date FY: 2022 ( Subtotal = $984,165 )
2022	2022	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Biology Research	000	3	7/22/2022	NON-COMPETING CONTINUATION	$984,165
														Subtotal = $984,165

Issue Date FY: 2021 ( Subtotal = $1,004,250 )
2021	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Biology Research	000	2	7/26/2021	NON-COMPETING CONTINUATION	$1,004,250
														Subtotal = $1,004,250

Issue Date FY: 2020 ( Subtotal = $1,004,250 )
2020	2020	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Biology Research	000	1	8/10/2020	NEW	$1,004,250
														Subtotal = $1,004,250

Grand Total All Awards = $4,326,714

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The role of clonal hematopoiesis in the development and therapy of myeloid malignancies

Award Number: R35CA253125

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2020

PERIOD OF PERFORMANCE END DATE: 11/01/2024

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