Relapsing visceral leishmaniasis in a HIV-1 infected patient with advanced disease.

Leishmaniasis, an intracellular protozoal infection in which tissue macrophages are targeted, is transmitted by female sandfly bite and occurs in 98 countries. Visceral leishmaniasis (VL) is the clinical form of leishmaniasis most frequently associated with HIV, especially in Europe. Both diseases have a synergistic detrimental effect on the cellular immune response.

Induction of myeloproliferative disorder and myelofibrosis by thrombopoietin receptor W515 mutants is mediated by cytosolic tyrosine 112 of the receptor.

Constitutively active JAK2V617F and thrombopoietin receptor (TpoR) W515L/K mutants are major determinants of human myeloproliferative neoplasms (MPNs). We show that a TpoRW515 mutation (W515A), which we detected in 2 myelofibrosis patients, and the Delta5TpoR active mutant, where the juxtamembrane R/KW(515)QFP motif is deleted, induce a myeloproliferative phenotype in mouse bone marrow reconstitution experiments. This phenotype required cytosolic Y112 of the TpoR.