An activating mutation in the transmembrane domain of the granulocyte colony-stimulating factor receptor in patients with acute myeloid leukemia

Chronic neutrophilic leukemia 2016: Update on diagnosis, molecular genetics, prognosis, and management

“…In this report, it was shown that mutated hematopoietic stem cells induced an MPN-like process in xenotransplantation and syngenic mouse bone marrow engraftment assays [22]. This mutation had previously been detected rarely as an acquired mutation in acute leukemia [23]. In the aforementioned family with hereditary chronic neutrophilia, clinicopathologic features for many affected satisfied the WHO diagnostic criteria for CNL.…”

“…Despite this, relatively few cases have been reported in the literature, reflecting the rarity of this disease and the older age of many affected. As such most of the information regarding this procedure is derived from single case reports and seven such cases, performed at ages 15,23,26,40,49,49, and 60 years, have been reported [5,32,37,45,57,79]. All patients received myeloablative conditioning (cyclophosphamide and total body irradiation), most had sibling donors, although two more recent cases received matched unrelated transplants [57,79].…”

Active Conformation of the Erythropoietin Receptor

“…We hypothesized that certain mutations in this region could mimic the activated dimeric state of EpoR, thus supporting the survival and proliferation of erythroid progenitors in the absence of Epo. A few activating mutations in the transmembrane and juxtamembrane domain have been identified in other cytokine receptors (15)(16)(17), but there has been no systematic attempt to identify them in EpoR.…”

Effects of the leukemia-associated AML1-ETO protein on hematopoietic stem and progenitor cells

“…Mutations in the GM-CSF receptor have not been reported in AML patients, whereas mutations in the G-CSF receptor (that truncate its intracellular tail) have been observed in AML and in particular, in children with severe congenital neutropenia who receive chronic, life-sustaining treatment with G-CSF. Such G-CSF receptor mutations have been shown to promote the development of leukemia in mouse models (Forbes et al, 2002).…”