# Role of Protein Kinase C Mutations in Adult T-Cell Leukemia

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2022 · $216,476

## Abstract

Abstract - Role of Protein Kinase C Mutations in Adult T-Cell Leukemia
 Human T-cell leukemia virus type 1 (HTLV-1) is the cause of a T cell lymphoproliferative disorder, designated
adult T-cell leukemia lymphoma (ATL). This is a highly refractory malignancy, lacking effective treatment
approaches, with a long-term survival rate of less than four percent. The current project exploits our exciting new
discovery of frequent, recurrent mutations in ATL cells in mediators of the T cell receptor (TCR) pathway including
phospholipase C γ1 (PLCγ1), protein kinase Cβ (PRKCβ), caspase recruitment domain family member 11
(CARD11), and interferon regulatory factor 4 (IRF4), and resultant nuclear factor κB activation and high level
expression of N-Myc. This proposal focuses specifically on possible gain-of-function mutations in PRKCβ in ATL,
the most frequent recurrently mutated gene in ATL, with mutation D427N accounting for more than 70% of these
PRKCβ mutations. First, we will determine 1) if PRKCβ mutation D427N promotes proliferation of T cells in mice,
if T cell proliferation in this setting can be inhibited with PRKCβ inhibitor, midostaurin, and we will identify
downstream gene targets of PRKCβ activation in this setting. Second, we will determine if PRKCβ D427N is
critical for proliferation of ATL cells in immunodeficient mice, and if ATL growth in mice can be inhibited by
midostaurin. We expect this study will provide promising new insights into effective therapy for ATL, which could
have relevance to other lymphoproliferative disorders.

## Key facts

- **NIH application ID:** 10322134
- **Project number:** 5R21CA255095-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Lee Ratner
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $216,476
- **Award type:** 5
- **Project period:** 2021-01-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10322134

## Citation

> US National Institutes of Health, RePORTER application 10322134, Role of Protein Kinase C Mutations in Adult T-Cell Leukemia (5R21CA255095-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10322134. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*