Melatonin nanoparticles inhibit mutant hematopoiesis and restore bone marrow architecture in myeloproliferative neoplasms

Myeloproliferative neoplasms (MPN) are chronic blood disorders marked by uncontrolled growth of blood cells, inflammation, oxidative stress, and damaging changes in bone marrow architecture. Scientists investigated whether melatonin (MT) and liposomal melatonin nanoparticles (nano-MT) could help treat these conditions.

In preclinical models, MT effectively stopped the growth of certain blood cells and stem cells compared to healthy cells. The treatment caused more cell death, lower levels of harmful chemicals called reactive oxygen species, and reduced sugar usage by the cells, without relying on MT's known receptor activity. Analyzing the cells' genes revealed that MT turned off certain genes linked to cell growth, DNA repair, harmful chemical production, and sugar metabolism.

When applied to cultures of blood-forming cells, MT reduced the production of connective tissue cells called stromal cells, which are involved in forming bone marrow fibrosis. In a mouse model of MPN, nano-MT efficiently reached the spleen and bone marrow. Notably, it lowered red blood cell production, increased the number of blood-forming cells, and reduced inflammation markers.

Micro-CT scans and tissue samples revealed that nano-MT restored the normal structure of bone marrow, reduced bone marrow hardening, and decreased spleen size. Importantly, it also increased the levels of red blood cells, hemoglobin, and platelets. These improvements suggest that nano-MT could restore normal blood cell counts and functions. When combined with another drug called ruxolitinib, nano-MT further reduced certain blood cell counts, easing the symptoms of MPN.

Overall, these findings show that (nano-)MT has the potential to treat MPN and restore the normal architecture of bone marrow by targeting various pathways involved in the disease. This study provides the first evidence of a therapeutic benefit for nano-MT in MPN and lays the groundwork for further research to explore its potential as a treatment.