The Hairy Cell Leukemia Foundation and Leukemia & Lymphoma Society are collaborating to invest $5-7 million in new research over 5 years to strengthen our understanding of the molecular basis of Hairy Cell Leukemia (HCL), develop better therapies, and optimize outcomes for patients. This new research program is called Hairy Cell Leukemia 2030 (HCL2030).

Goals of HCL2030

• Uncovering novel features of cHCL biology,

• Understanding the distinguishing features of HCLv and apply that knowledge in the clinic,

• Translating new medical knowledge to clinical application and testing novel treatments in patients through clinical trials, and

• Applying the HCL registry created by HCLF to examine long-term outcomes and quality of life.

The overarching goals of HCL2030 are to improve patient outcomes and find a cure!

Download the Request for Proposals (RFP)

Research Focus Areas

While investigators are encouraged to submit proposals in any clinical or biological topics related to hairy cell leukemia, certain research areas will be prioritized.

On the clinical side, these include a) studies of innovative treatments for situations of high unmet medical need that require accurate diagnosis and characterization of the HCL-like disease spectrum, including classical HCL and HCLv; b) novel strategies to treat infections associated with HCL; and c) risk stratification and development of targeted treatments.

Equally important, we also seek a deeper understanding of the disease and will support studies focused on a) uncovering novel features of HCL biology and cellular vulnerabilities; b) investigations into mechanisms of HCL relapse and therapy resistance; and c) efforts to establish and validate in vitro and in vivo models of the disease. Such fundamental studies should be focused toward translational potential and driven ultimately by the goals of improved patient outcomes and reduction or elimination of disease.

Examples of projects of potential interest:

• Studies of cellular activities that underlie the behavior and vulnerabilities of HCL cells including the role of novel signaling pathways, epigenetic alterations, metabolic vulnerabilities, cellular interaction with the microenvironment, and regulation of aberrant cell morphology,

• Development of novel immunotherapies targeting unique or abundant HCL cell surface markers,

• Exploration of novel combination therapies with the potential to provide improved efficacy and extended relapse-free survival,

• Studies into the molecular basis of HCLv and alternative therapies to treat the disease,

• Investigations into resistance mechanisms including immune evasion, resistant clone evolution, failure of B-RAF or RAS pathway inhibitors, and cellular changes underlying disease relapse,

• Development and use of in vitro or in vivo systems to model HCL, including novel cell culture systems, patient-derived xenographs (PDX) and other animal models, and

• Development and evaluation of reliable surrogate blood-borne markers to predict progression-free survival, detect early relapses, or justify early interception in the 10-20% of “watch and wait” patients with HCL or those previously treated for HCL.

Call for Proposals

Grant Funding Mechanisms

We will support research advances via an investigator-initiated and peer-reviewed granting mechanism.

Two grant types will be awarded:

Laboratory to Clinical Research Grants (LCRG)

• Projects focused on translational research, including basic research if justified, that has relevance to therapeutic development

• Project led by a single Principal Investigator (PI) but may have one co-PI

• 3 years of support, with the third-year funding dependent on progress assessment at end of year 2

• Cost not to exceed $250,000/year ($750,000 total), including indirect costs

• Indirect costs (institutional overhead) capped at 10% of the total grant award

• Funds intended for flexible use that may include salaries (capped at 40%), equipment, supplies, or personnel

Collaborative Team Grants (CTG)

• Projects focused on the development and implementation of novel clinical trials

• Program activities can include pre-clinical development and correlative studies

• Either one trial with supporting correlative work or multiple projects with related but distinct approaches that contribute to a transformational advance in the treatment of HCL

• Up to 4 investigators (Project Leaders) led by a Program Director (PD)

• Funding for core facilities (e.g., chemistry, genomics, animal models, computation) may be included but not exceed 20% of the total cost

• Up to 4 years of support

• Cost not to exceed $625,000/yr ($2,500,000 total), including indirect costs; more focused applications may not require the maximum amount of funding

• Indirect costs (institutional overhead) capped at 10% of the total grant award

􀂃 Funds intended for flexible use may include salaries (capped at 40%), equipment, supplies, or personnel

􀂃 Demonstration of other financial support for the proposed work from industry or other foundations, which leverages funding provided by HCLF and LLS is encouraged

• A Patient Involvement Plan (PIP) is required for CTG grants that include a clinical trial.

Application Process

Applications will be evaluated based on clearly stated hypotheses, scientific rationale, innovation, feasibility, preliminary data, track-record of the investigators, and potential benefit to HCL patients. There are two phases of the application process. In the first phase, the letter of intent (LOI) will be evaluated for eligibility, and all eligible applicants will be invited to submit a Full Application. Applications will be reviewed by a committee composed of experts in HCL or blood cancer biology and therapeutics. Final funding decisions will be based on the committee evaluation, priorities of HCLF and LLS, and the availability of funds. We may request further clarification of the application prior to making a final decision.

Both LOI and Full Application submissions must be made electronically through the LLS Research Portal.

Detailed instructions for preparation of the LOI and Full Application can be found in the HCL2030 Guidelines and Instructions through the LLS website. The guidelines and instructions are also available for download below.

Collaborative Team Grants (CTGs)

Laboratory to Clinical Research Grants (LCRGs)

Key Dates

Call For Proposals: July 1, 2025

Letter of Intent Due: September 3, 2025

Full Application Deadline: November 21, 2025

Grant Term Begins: April 1, 2026

Key References

Andritsos LA, Anghelina M, Neal J, et al.  Development of a distributed international patient data registry for hairy cell leukemia. Leuk Lymphoma. 2022. 63:3021-3031.

Bhagwat AS, Torres L, Shestova O, et al. Cytokine-mediated CAR T therapy resistance in AML. Nat Med. 2024. 30:3697-3708.

Braun DA, Moranzoni G, Chea V, et al. A neoantigen vaccine generates antitumour immunity in renal cell carcinoma. Nature. 2025. 639:474-482.

Chung SS, Kim E, Park JH, et al. Hematopoietic stem cell origin of BRAFV600E mutations in hairy cell leukemia. Sci Transl Med. 2014. 6:238ra71.

Eton EO, Ganesan S, Murray RM et al. Transcriptomic and Epigenomic Landscape of Hairy Cell Leukemia at Single-Cell Resolution. Blood 2024. 144 (supplement 1): 1604.

Falini B and Tiacci E. Hairy-Cell Leukemia. N Engl J Med. 2024. 391:1328-1341.

Kim WJ, Crosse EI, de Neef E et al. Cell Mis-splicing-derived neoantigens and cognate TCRs in splicing factor mutant leukemias. Cell. 2025. in the press.

Sethna Z, Guasp P, Reiche C et al. RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer. Nature. 2025. 639:1042 1051.

Troussard X and Maitre E. Untangling hairy cell leukaemia (HCL) variant and other HCL-like disorders: Diagnosis and treatment. J Cell Mol Med. 2024. 28:e18060.

Yamaguchi, K, Abdelbaky S, Arons E. et al. DNA Methylation-Based Classification of Hairy Cell Leukemia and Splenic B Cell Lymphoma. Blood. 2023. 142 (Supplement  1): 174.