Editors' ChoiceHEMATOLOGY

Stronger together

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Science Translational Medicine  02 Nov 2016:
Vol. 8, Issue 363, pp. 363ec175
DOI: 10.1126/scitranslmed.aaj2090

Although allogeneic hematopoietic stem cell transplant (HSCT) can cure high-risk leukemia and other hematological malignancies, patients may trade one serious disease for another. After HSCT, some patients suffer poor graft function characterized by low white blood cell (WBC), red blood cell (RBC), and platelet counts. Persistent poor graft function causes dependence on platelet and RBC transfusions and a high risk of life-threatening infections. No targeted treatment exists for this condition. Endothelial progenitor cells (EPCs)—hematopoietic stem cell–derived cells that form part of the bone marrow microenvironment—display impaired function in patients with poor graft function. Now, Shi and colleagues have investigated atorvastatin, a cholesterol-lowering medication, as a possible treatment for poor graft function.

The authors isolated bone marrow EPCs from HSCT recipients with poor graft function and good graft function, as well as from bone marrow donors serving as healthy controls. EPCs from subjects with poor graft function demonstrated lower migration and tube formation in vitro, suggesting that they are less capable of supporting bone marrow function. The poor-graft-function EPCs also had higher intracellular reactive oxygen species, stress-response proteins, and apoptosis rates. Treatment of poor-graft-function EPCs with atorvastatin improved their migration, tube formation, and apoptosis rate, although these functions remained more impaired than in the good-graft-function and healthy-control EPCs.

The bone marrow microenvironment is a critical part of hematopoietic stem cell function and dysfunction. To determine whether EPC dysfunction inhibits blood cell synthesis in the bone marrow, the authors cocultured poor-graft-function EPCs with bone marrow stem cells from healthy controls. The poor-graft-function EPCs impaired growth and differentiation of the bone marrow stem cells and, again, atorvastatin treatment resulted in improvement.

Looking forward, atorvastatin could be incorporated into a clinical trial to support hematopoietic stem cell engraftment, either for primary prevention of poor graft function or as a rescue treatment. However, statins have side effects that can overlap with HSCT sequelae, especially hepatocellular injury; therefore, thorough evaluation in HSCT recipients will be critical to determine safety and efficacy.

M.-M. Shi et al., Atorvastatin enhances endothelial cell function in post transplant poor graft function. Blood 10.1182/blood-2016-03-702803 (2016). [Abstract]

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