Bone Marrow Receptor Opens Door To New Therapy For a Pediatric Leukemia

Susan Schwab, PhD Assistant professor at NYU Langone Skirball Institute of Biomolecular Medicine MedicalResearch.com Interview with:
Susan Schwab, PhD
Assistant professor at NYU Langone
Skirball Institute of Biomolecular Medicine

Medical Research: What is the background for this study? What are the main findings?

Dr. Schwab:  T cell acute lymphoblastic leukemia (T-ALL) remains a devastating pediatric disease.  Roughly 20% of children do not respond to current therapies.  Furthermore, metastasis to the central nervous system is common in T-ALL, and intrathecal chemotherapy, even when successful at eradicating the cancer, causes serious long-term cognitive side-effects.

Here we report that the chemokine receptor CXCR4 is essential for T cell acute lymphoblastic leukemia progression in both mouse and human xenograft models of disease.  Consistent with sustained disease remission in the absence of CXCR4, loss of CXCR4 signaling results in decreased levels of c-Myc, which is required for leukemia initiating cell activity.   T-ALL cells reside near cells generating the CXCR4 ligand CXCL12 in the bone marrow, and our data suggest that vascular endothelial cells may be an important part of the T-ALL niche.

Medical Research: What should clinicians and patients take away from your report?

Dr. Schwab:  The importance of CXCR4 in T-ALL was unexpected because CXCR4 plays only limited roles in normal T cell development and peripheral T cell maintenance.  Yet because several potent and well-tolerated CXCR4 antagonists are in clinical trials for other blood cancers, this finding may be rapidly translated into improved therapy for T cell acute lymphoblastic leukemia patients.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Schwab: One very high priority is to perform further preclinical testing of CXCR4 antagonists in T-ALL, using a wider spectrum of patient samples.

A second priority is to understand why CXCR4 is indispensable for T-ALL, which would help identify patients who would most benefit from CXCR4 antagonism.

Citation:

CXCL12-Producing Vascular Endothelial Niches Control Acute T Cell Leukemia Maintenance

Pitt, Lauren A. et al.

Cancer Cell , Volume 27 , Issue 6 , 755 – 768

 

Susan Schwab, PhD, Assistant professor at NYU Langone,  Skirball Institute of Biomolecular Medicine (2015). Bone Marrow Receptor Opens Door To New Therapy For a Pediatric Leukemia