AsianScientist (Sep. 2, 2015) – Researchers have found a novel nutrient uptake process that maintains the activity of murine chronic myelogenous leukemia (CML) stem cells. Their results, published in Nature Communications, show that pharmacological inhibition of nutrient uptake can decrease CML stem cell activity in vivo, thus pointing towards a potential therapeutic target for CML therapy.
CML stem cells, the cellular source of a vast majority of CML cells, are thought to be responsible for the recurrence of CML following the currently used tyrosine-kinase inhibitor (TKI) therapy.
“Although TKIs such as the first-generation TKI imatinib mesylate and the second-generation TKIs dasatinib and nilotinib have markedly improved the prognosis of patients with chronic phase CML, a cure remains elusive,” said Dr. Kazuhito Naka, an associate professor at Hiroshima University.
“To completely eradicate CML stem cells and CML, TKIs may have to be coupled with novel therapeutics targeting alternative mechanisms.”
Naka, Professor Takihara Yoshihiro from Hiroshima University, and an international group of researchers including Professor Kim Seong-Jin from CHA University and Professor Kato Yukio from Kanazawa University have surveyed metabolites specific to CML stem cells, isolated from a mouse model of CML.
They found that CML stem cells accumulate significantly higher levels of certain dipeptide species than do normal hematopoietic stem cells. Once internalized, these dipeptide species act as nutrients for the CML stem cells and play a role in CML stem cell maintenance. Importantly, an inhibitor of the dipeptide uptake blocks CML stem cell activity in mice.
“Our proposed approach of using inhibitors to shut down a key nutrient uptake process specific to CML stem cells, in combination with TKI therapy, may thus provide concrete therapeutic benefits to patients with CML. It will open up a novel avenue for curative CML therapy,” Naka explained.
Source: Hiroshima University.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.