Acute myeloid leukemia (AML) is a malignant clonal disease originating from myeloid hematopoietic stem/progenitor cells. It is a quickly progressing disease in which too many abnormal white blood cells are found in the bone marrow. AML is the second most common form of leukemia in children after acute lymphoblastic leukemia (ALL), and notoriously difficult to cure, due to its resistance to standard treatments.
Now, scientists at the Children’s Cancer Institute in Australia report they have discovered a new and improved way to treat the poor-prognosis acute myeloid leukemia. Their study, “Targeting RSPO3-LGR4 Signaling for Leukemia Stem Cell Eradication in Acute Myeloid Leukemia,” is published in Cancer Cell and led by Jenny Wang, PhD, senior lecturer and ARC future fellow at the Faculty of Medicine, UNSW Australia and a group leader of cancer and stem cell biology at Children’s Cancer Institute.
The scientists investigated what they believe is the culprit for AML, leukemia stem cells (LSCs).”Leukemia stem cells have their own protective mechanisms that make them resistant to anticancer drugs,” stated Wang.”After chemotherapy, if even one leukemic stem cell is left alive, it can regenerate and the disease can come back.” Stem cells are not only capable of giving rise to different types of cells, but also of cloning themselves indefinitely in a process known as self-renewal.
Scientists attempted a new treatment approach by targeting the leukemia stem cells and disrupting the self-renewal process. Using a mice model with growing cancer cells taken directly from patients with AML, the scientists used an antibody treatment to disrupt the interaction of two molecules, RSPO2/3 and RSPO-LGR4. RSPO-LGR4 upregulates key self-renewal genes and is essential for LSC self-renewal in a subset of AML. RSPO2/3 serves as stem cell growth factors to block differentiation and promote proliferation of primary AML patient blasts.
“Blocking the RSPO3-LGR4 interaction by clinical-grade anti-RSPO3 antibody (OMP-131R10/rosmantuzumab) impairs self-renewal and induces differentiation in AML patient-derived xenografts but does not affect normal hematopoietic stem cells, providing a therapeutic opportunity for HOXA9-dependent leukemia,” the researchers wrote.
The scientists discovered that the antibody reduced the amount of leukemia, and prevented new leukemia cells from growing. The antibody treatment also did not harm healthy stem cells, which children treated for AML require to reconstitute their blood system after treatment.
Scientists are optimistic in the therapy progressing to clinical trials and hope it will prove to be an effective therapy in children with AML.
Originally published by
GEN - Genetic Engineering & Biotechnology News
June 22, 2020