Scientists from NYU Langone Medical Center have revealed a breakthrough on defense leukemia, it may help develop new targeting therapy on leukemia. This study was published on Cancer Cell.

Acute lymphoblastic leukemia(ALL) is the most common of childhood cancers, and 15%-20% of ALL cases are T lineage(T-ALL). A quarter of childhood T-ALL patients relapse within 5 years of treatment and receive a dismal prognosis. Factors predicting poor survival of relapsed childhood ALL patients include T lineage disease and isolated bone marrow involvement, both of which have a less than 25% five-year survival rate.

Increasing evidence suggests that leukemic stem cells actively engage in crosstalk with the bone marrow microenvironment to regulate their proliferation and survival. Similarities between LICs and hematopoietic stem cells(HSCs) have raised the hypothesis that LICs require a specialized microenvironment to survive and that disrupting this niche may be a promising therapeutic strategy.

While much is known about the cell-intrinsic factors that support leukemia progression, little is understood about the role of the microenvironment. T cell acute lymphoblastic leukemia(T-ALL) cells have commonly acquired mutations in pathways downstream of surface receptors that regulate differentiation, survival, and proliferation in response to environmental cues, and it is unknown whether this frees T-ALL from dependence on a putative leukemic niche.

In this study, researchers identify CXCL12-producing vascular endothelial cells as a require component of a T-ALL niche. Moreover, they show that targeting CXCL12/CXCR4 signaling after disease onset dramatically reduces T-ALL burden in murine and xenograft models of disease, suggesting a powerful therapeutic approach for this devastating cancer.

Reference:

 Pitt L A, Tikhonova A N, Hu H, et al. CXCL12-producing vascular endothelial niches control acute T cell leukemia maintenance[J]. Cancer cell, 2015, 27(6): 755-768.