Genetic events associated with progression to acute myeloid leukemia after a JAK2-mutant MPN. (A) Assessment of JAK2 copy number in 7 JAK2-mutant leukemias with the use of a real-time PCR assay; samples from healthy persons and cell lines known to harbor a deletion of 9p (MDA-MB-361 and NB16) or multiple copies of JAK2 (HEL) are shown as controls. (B) Expression of total JAK2 measured by real-time PCR normalized to normal CD34⁺ cells showing a 12-fold increase in relative JAK2 expression in patient 6. (C) Mutation genotyping from 5 patients progressing to acute leukemia showing that, whereas RUNX1 mutations were acquired at the time of progression to AML, NRAS mutations may be associated with the preceding MPN. Mut indicates mutant; WT, wild-type; grans, purified granulocytes; and BM, bone marrow.