Thursday, January 1, 2026 1/1/2026

The Biological Consequences of Age-related Clonal Hematopoiesis

Award Number: R01HL156144
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/10/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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The Biological Consequences of Age-related Clonal Hematopoiesis - Clonal hematopoiesis of indeterminate potential (CHIP) defined as acquisition of somatic mutations in hematopoietic cells is a common age-related condition. The prevalence of CHIP exceeds 12% over all age groups and nearly 50% for subjects older than 85 years. Since somatic mutations frequently affect putative cancer drivers the malignant transformation to myelodysplasia or leukemia is an obvious concern. Even though CHIP is relatively common, the risk of progression to clinically apparent disease is low (<1% per year) and the exact mechanism of progression is largely unknown. Thus, the appropriate risk-stratification of patients remains challenging. In addition to its leukemogenic potential, CHIP is also an independent risk factor of chronic inflammation, cardiovascular disease and has been associated with inferior outcome in general population and in patients with solid tumors. One approach to address the clinical impact of clonal hematopoiesis is to identify and prospectively follow a large cohort of individuals with CHIP. However, this approach would require large number of subjects and long follow-up period. While the long-term prospective studies are underway we propose to study the natural history and clinical consequences and the mechanism of clonal expansion of CHIP in allogeneic blood or marrow transplantation (alloBMT) setting. We have previously published that clinically silent clones (under homeostatic conditions within the donor) expand and are selected for during the enhanced proliferation and self-renewal required to re-establish hematopoiesis in the recipient; this implies that alloBMT greatly hastens the natural history of CHIP, which should allow us to capture the genetic evolution, clonal dynamics, and clinical sequelae of CHIP in an accelerated time-frame. We will 1) determine the oncogenic potential and non-malignant adverse outcome of donor-derived CHIP in alloBMT recipients. Studying the cohort of 1,857 bone marrow donors above the age of 40 as well as serial samples and clinical data we will better define the oncogenic potential of low-frequency clones and distinguish true disease drivers from background genetic events related to aging and examine the role of donor CHIP on non-malignant adverse events in alloBMT recipients; 3) elucidate the epigenetic aberration and cellular pathway involved in clonal growth advantage; 3) determine the impact of CHIP on the incidence of subclinical solid tumors studying nearly 10,000 females enrolled on DETECT trial and define the role of CHIP in tumor development and progression. The aforementioned approach will allow us 1) to better define the oncogenic potential and epigenetic aberrations in pre-malignant clones as well as non-malignant consequences of donor CHIP in alloBMT recipients; 2) our prospective study will not only provide an insight into the risk stratification of patients with CHIP but will also provide a very important human model for studying clonal evolution and leukemogenesis in vivo. 3) we will better define the impact of CHIP on subclinical tumors and the results from our study may result in implementation of most appropriate therapies in order to avoid therapy-related malignancies and cardiovascular toxicities.


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 = $0 )
2026	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	5	12/3/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $409,375 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	5	1/25/2025	NON-COMPETING CONTINUATION	$409,375
														Subtotal = $409,375

Issue Date FY: 2024 ( Subtotal = $409,375 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	4	2/10/2024	NON-COMPETING CONTINUATION	$409,375
														Subtotal = $409,375

Issue Date FY: 2023 ( Subtotal = $409,375 )
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	3	1/25/2023	NON-COMPETING CONTINUATION	$409,375
														Subtotal = $409,375

Issue Date FY: 2022 ( Subtotal = $409,375 )
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Blood Diseases and Resources Research	001	2	6/13/2022	NON-COMPETING CONTINUATION	$40,937
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	2	2/11/2022	NON-COMPETING CONTINUATION	$368,438
														Subtotal = $409,375

Issue Date FY: 2021 ( Subtotal = $409,375 )
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	1	2/9/2021	NEW	$368,438
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Blood Diseases and Resources Research	001	1	6/19/2021	NEW	$40,937
														Subtotal = $409,375

Grand Total All Awards = $2,046,875

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The Biological Consequences of Age-related Clonal Hematopoiesis

Award Number: R01HL156144

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/10/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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