Molecular characterization of de novo Philadelphia chromosome-positive acute myeloid leukemia

Philadelphia chromosome-positive (Ph+) acute myeloid leukemia (AML) is a controversial diagnosis, as others propose that it represents chronic myelogenous leukemia in blast phase (CML-BP). NPM1 mutations occur in 25-35% of patients with AML but are absent in patients with CML. Conversely, ABL1 mutations occur in 25% of imatinib-naive patients with CML-BP but are not described in patients with AML. We analyzed for NPM1 and ABL1 mutations in nine Ph+ patients with AML and five patients with CML-BP initially presenting in BP. In six cases of Ph+ AML, we screened for a panel of gene mutations using Sequenome (R) - based methods including AKT1, AKT2, AKT3, BRAF, EGFR, GNAQ, GNAS, IDH1, IDH2, KRAS, MET, NRAS, PIK3CA and RET. Two of nine (22%) patients with Ph+ AML had NPM1 mutations and were alive 36 and 71 months after diagnosis. All cases of Ph+ AML were negative for ABL1 and other gene mutations. One (20%) patient with CML-BP had ABL1 mutation; no patients had NPM1 mutations. These data suggest that Ph+ AML is distinct from CML-BP.