Ferumoxytol

Ferumoxytol is an FDA-approved ultrasmall superparamagnetic iron oxide preparation and iron replacement agent that exerts selective activity against leukemia cells with low ferroportin expression. Ferumoxytol increases intracellular iron levels, induces reactive oxygen species (ROS) production via the Fenton reaction, and triggers oxidative stress and cell death. Ferumoxytol reduces disease burden in mouse models and patient-derived leukemia models. As an MRI contrast agent, Ferumoxytol enables imaging of vascular lesions, tumors and lymph nodes. Ferumoxytol can be used in research related to acute myeloid leukemia and blast-phase chronic myeloid leukemia^[1]. In Vitro:Ferumoxytol (24 h) significantly increases intracellular iron levels in human AML cell lines with low FPN expression, but exerts no such effect on human AML cell lines with high FPN expression^[1].
Ferumoxytol (24-48 h) significantly reduces the viability of human acute myeloid leukemia (AML) cell lines and primary AML samples with low FPN expression, an effect mediated by oxidative stress, while human AML cell lines with high FPN expression are unaffected^[1].
Ferumoxytol treatment upregulates the antioxidant stress response genes *SLC7A11*, *HMOX1* and *GCLC* in human AML cell lines with low FPN expression, and the extent of upregulation varies among different cell lines; in contrast, the expression of the aforementioned antioxidant genes shows no change in human AML cell lines with high FPN expression, and no upregulation of inflammatory cytokine genes is observed in any AML cell lines^[1].
Ferumoxytol (24-48 h) significantly upregulates cytosolic and mitochondrial ROS levels in human acute myeloid leukemia (AML) cell lines with low FPN expression, and the increase in ROS levels correlates with decreased cell viability; in contrast, no significant change in ROS levels is observed in human AML cell lines with high FPN expression^[1]. In Vivo:Ferumoxytol (3-6 mg/kg; i.v., twice weekly; i.p., three times weekly) reduces leukemia blasts burden in the peripheral blood, bone marrow and spleen of mouse bcCML models, decreases the spleen index, and extends the median survival time by 8 days^[1].
Ferumoxytol (5 mg/kg; intravenous injection; twice weekly; for 4 consecutive weeks) selectively reduces the bone marrow engraftment rate of FPN-low-expressing AML PDX, without affecting FPN-high-expressing AML PDX or normal hematopoietic cells, and simultaneously induces oxidative stress in FPN-low-expressing leukemia cells^[1].