# The roles of SOCS5 in T-ALL migration and tissue infiltration

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2022 · $332,900

## Abstract

Aberrant regulation of cell migration confers malignant properties of cancer cells and plays a critical role
in leukemia progression and resistance. To date, very few molecules, including chemokine receptors have
been implicated in T-cell lineage acute lymphoblastic leukemia (T-ALL) migration and CNS disease and/or
relapse. The suppressors of the cytokine signaling (SOCS) family are known cytokine-inducible negative
regulators of signal transduction, but their roles in regulating cell migration remain poorly understood. While it
is clear that chemokine receptor signaling is important for T-ALL leukemogenesis and secondary organ
infiltration, the roles of intrinsic signaling mediators of cell migration have been understudied. SOCS5 is a
known regulator of JAK-STAT signaling and was shown to be involved in T-cell differentiation. We discovered
downregulation of SOCS5 gene expression levels in a subset of high-risk T-ALL. Our preliminary findings
provide strong evidence that silencing of SOCS5 expression enhances T-ALL cell migration and CNS
infiltration, and induces upregulation of genes involved in cell migration. The goal of this study is to address
how SOCS5 downregulation facilitates T-ALL migration leading to leukemic cell trafficking to the CNS. We
hypothesize that SOCS5 downregulation promotes T-ALL migration leading to extramedullary tissue infiltration.
Our rationale is that given functional similarities between hematopoietic stem cells and leukemic cells such as
the ability to migrate, genes involved in T-cell development may contribute to enhancing aberrant signaling
leading to increased migration and leukemia progression. Using T-ALL patient derived xenografts we will
determine the roles of SOCS5 in the regulation of T-ALL cell migration. In Aim 1, we will investigate the
mechanism by which SOCS5 regulates expression of the CXCR3 chemokine receptor in migrating T-ALL cells.
In our Aim 2, we propose to study the roles of SOCS5 downregulation in promoting T-ALL migration.
Specifically, we will focus on the interaction between SOCS5 and LCK, a Src family kinase, in regulating T-ALL
migration. Finally, in Aim 3, we will investigate how changes in SOCS5 expression affect T-ALL migration to
medullary and extramedullary sites. The goal will be to establish the importance of SOCS5 downregulation in
leukemia migration and infiltration of peripheral tissues, including the CNS. We expect to show the migratory
potential of SOCS5 downregulation in T-ALL and establish the importance of negative regulators of signal
transduction in T-ALL. Studying T-ALL migration can provide important information related to the mechanisms
that cause leukemia survival and CNS infiltration, and will contribute to the development of novel treatment
approaches.
 .

## Key facts

- **NIH application ID:** 10434801
- **Project number:** 5R01CA237165-05
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Ksenia Matlawska-Wasowska
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $332,900
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434801

## Citation

> US National Institutes of Health, RePORTER application 10434801, The roles of SOCS5 in T-ALL migration and tissue infiltration (5R01CA237165-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10434801. Licensed CC0.

---

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