These mutations include JAK2, CALR and MPL mutations as the main disease drivers, mutations driving clonal expansion, and mutations that contribute to progression of chronic MPNs to myelodysplasia and acute leukemia.
In this study (ASPIRE), we aimed to assess eltrombopag, an oral thrombopoietin receptor agonist, for thrombocytopenia (grade 4) treatment in adult patients with advanced MDS or AML.
Because MPL is expressed on hematopoietic cells, eltrombopag use in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) might enhance leukemic proliferation.
DNA was available in 138 patients and mutation screening revealed 20 cases with JAK2, 6 with IDH, and 3 with MPL mutations; JAK2 and MPL mutations were seen mostly in MPN or "MDS with isolated del(5q)" whereas IDH mutations were frequent in other MDS variants.
We report a patient with a JAK2 V617F-negative myeloproliferative/myelodysplastic syndrome who had abnormal megakaryocytic pSTAT5 expression and a MPLW515L mutation.
Expression of the thrombopoietin receptor, c-mpl, has been recently suggested to represent an adverse prognostic factor in myelodysplasia and acute myeloid leukemia (AML).
The gene for the thrombopoietin receptor, c-mpl, has been shown to be overexpressed at the mRNA level in acute myeloid leukemia (AML) and myelodysplastic syndrome.
Finally, rHuMGDF-induced blast cell proliferation correlated with elevated expression of c-MPL, previously identified as a bad prognosis factor in MDS.