# Circulating biomarkers of ALK+ anaplastic large cell lymphoma

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $288,649

## Abstract

Project Summary
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase encoded by the ALK gene located on 5q35.
Structural alterations including translocations, copy number gains and activating mutations targeting ALK
occur in many types of human cancer, including lung cancer, non- Hodgkin lymphomas, Spitzoid
melanocytic lesions, neuroblastoma and inflammatory myofibroblastic tumor. In over 80% of pediatric
anaplastic large cell lymphoma (ALCL), the most common form of mature T cell lymphoma in this population,
the chromosomal aberration t(2;5)(p23;q35) results in the expression of the constitutively active tyrosine
kinase NPM-ALK. NPM-ALK positive lymphoma has served as a model for understanding ALK-mediated
oncogenesis and development of targeted therapies, thus NPM-ALK related studies carry profound
implications for the cancer field in general. Unfortunately, even with current intensive combined
chemotherapy, approximately 30% of patients experiences disease progression or recurrence within two
years of treatment. However, clinical or genetic factors that cause ALCL relapse are not known.
Furthermore, prognostic biomarkers that can be easily obtained using non-invasive methods have not been
clearly defined in patients receiving targeted therapies in ALCL. Our central hypothesis is that sensitive and
specific quantitative assessment of circulating NPM-ALK transcript using digital droplet (dd)PCR in
conjunction with plasma levels of ALK auto- antibody will serve as unique disease-specific biomarkers that
will provide an opportunity for assessment of response to therapy and lead to prognostic biomarkers that
may identify patients with high risk for relapse. Using plasma samples from uniformly treated patients
enrolled in a Children's Oncology Group (COG) Phase II study of Brentuximab Vedotin and Crizotinib with
newly diagnosed ALCL, we address our hypothesis through the following specific aims: 1) Determine the
utility of ddPCR for minimal disease detection and disease monitoring in ALK+ ALCL, 2) Determine the
prognostic utility of anti-ALK immune response in ALK+ ALCL 3) Investigate the prognostic significance of a
multivariate model combining ddPCR and immune response to ALK in patients with ALK+ ALCL. The
development of sensitive and precise assessment of minimal disseminated disease and/or minimal residual
disease will play an important role in management of patients with ALK+ ALCL and facilitate decisions about
discontinuation of treatment and identifying patients at risk of relapse/progression.

## Key facts

- **NIH application ID:** 10896343
- **Project number:** 5R01CA255350-05
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Megan S. Lim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $288,649
- **Award type:** 5
- **Project period:** 2022-10-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896343

## Citation

> US National Institutes of Health, RePORTER application 10896343, Circulating biomarkers of ALK+ anaplastic large cell lymphoma (5R01CA255350-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10896343. Licensed CC0.

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