Myeloproliferative disorder induced in vivo by Δ5TpoR and TpoRW515A mutants. (A) Sequencing of genomic DNA isolated from peripheral blood granulocytes of primary myelofibrosis patients. A W515L (TGG→TTG) mutation was identified in TpoR from patient 64. A W515A (TGG→GCG) mutation was detected in TpoR from patient 66. (B) Shown is the location of the amphipathic K(R)WQFP motif at the junction between the TpoR transmembrane (TM) and cytosolic domains. (C) Peripheral blood counts, taken 45 days after reconstitution with bone marrow cells expressing the indicated TpoR variants, demonstrated that Δ5TpoR and TpoRW515A induce a rapid myeloproliferative disease. (D) Hematocrit values (%) were determined 45 days for mice reconstituted with bone marrow cells expressing the indicated TpoR constructs.