Obesity has reached epidemic proportions, affecting over a third of the world’s population. Obesity is a major risk factor in many comorbidities including cancer, and those who are obese often have a low level of chronic inflammation, indicating an impaired immune system. This is particularly true for B-Acute Lymphoblastic Leukemia (B-ALL), the most common type of cancer in children. Mortality rates for obese children with B-ALL are 30% greater compared to their peers that fall within the recommended weight ranges.
The link between obesity in children and B-ALL is not well understood and remains under-investigated. It is thought that fat cells (adipocytes) may be potent producers of pro-inflammatory cytokines and chemokines, which can protect leukemic cells against certain chemotherapeutic agents. Curtis Henry is examining how obesity can have such a negative impact on B-ALL prognosis. His preliminary data show that human B-leukemia cells cluster when exposed to adipocyte-conditioned media, reducing their proliferation and shielding them from commonly used chemotherapies. Dr. Henry and his team aim to identify the factors secreted by adipocytes that induce chemoresistance of the leukemic cells. This will help determine whether targeting soluble factors in the adipocyte secretome can help improve chemotherapy treatment.
Lee M, Hamilton JAG, Talekar GR, Ross AJ, Michael L, Rupji M, Dwivedi B, Raikar SS, Boss J, Scharer CD, Graham DK, DeRyckere D, Porter CC, Henry CJ. Obesity-induced galectin-9 is a therapeutic target in B-cell acute lymphoblastic leukemia. Nat Commun. 2022.
Lee M, Geitgey DK, Hamilton JAG, Boss JM, Scharer CD, Spangle JM, Haynes KA, Henry CJ. Adipocyte-mediated epigenomic instability in human T-ALL cells is cytotoxic and phenocopied by epigenetic-modifying drugs. Front Cell Dev Biol. 2022.
Geitgey DK, Lee M, Cottrill KA, Jaffe M, Pilcher W, Bhasin S, Randall J, Ross AJ, Salemi M, Castillo-Castrejon M, Kilgore MB, Brown AC, Boss JM, Johnston R, Fitzpatrick AM, Kemp ML, English R, Weaver E, Bagchi P, Walsh R, Scharer CD, Bhasin M, Chandler JD, Haynes KA, Wellberg EA, Henry CJ. The ‘omics of obesity in B-cell acute lymphoblastic leukemia. J Natl Cancer Inst Monogr. 2023.