A new drug target to overcome obesity-induced chemoresistance in B-acute lymphoblastic leukaemia

March 2022 Prevention Nalinee Pathak

A team of researchers have shown that upregulation of Galectin-9 (GAL-9) on human B-acute lymphoblastic leukaemia (B-ALL) cells can be targeted with antibody-based therapies. This strategy can be employed to overcome obesity-induced chemoresistance in B-cell ALL patients. The findings from this study were reported in the journal Nature communications.

Obesity rates are rapidly rising globally, with a large population (40%) expected to suffer from weight-related issues by 2030. In addition to complications related to obesity, what is alarming is that obesity increases mortality rates in various types of cancers, including leukaemia. The connection between obesity and poorer clinical outcomes in cancer patients is largely attributed to the accumulation of adipocytes, which are believed to alter the pharmacokinetics of treatment drugs. However, the direct impact of an adipocyte-enriched microenvironment on hematopoiesis and haematological malignancies is still unexplored.

Poor survival

The research team found that adipocytes induce expression of a surface marker, GAL-9, on human B-ALL and expression of this gene protects cancer cells from environmental and chemotherapy-induced cytotoxicity. Notably, the GAL-9 surface expression was higher on B-ALL cells from obese pediatric patients than lean patients. Moreover, higher GAL-9 expression was associated with poor survival outcomes. Antibody-mediated targeting of GAL-9 on B-ALL cells induced cytotoxicity in B-ALL cells in vitro. Further, the ╬▒GAL-9 antibody treatment significantly extended the survival of obese mice with aggressive B-ALL.

In conclusion, the study demonstrates the association of GAL-9 surface markers with obesity and adverse clinical outcomes in B-cell ALL patients. Thus, GAL-9 is an attractive therapeutic target for patients with B-Cell ALL.

Reference

Lee M, Hamilton JAG, Talekar GR, Ross AJ, Michael L, Rupji M, et al. Obesity-induced galectin-9 is a therapeutic target in B-cell acute lymphoblastic leukemia. Nat Commun [Internet]. 2022;13(1):1157. Available from: https://doi.org/10.1038/s41467-022-28839-y

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