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(®)-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.
Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. skonople@mdanderson.org
Sergej
S
Konoplev
C Cameron
CC
Yin
Steven M
SM
Kornblau
Hagop M
HM
Kantarjian
Marina
M
Konopleva
Michael
M
Andreeff
Gary
G
Lu
Zhuang
Z
Zuo
Rajyalakshmi
R
Luthra
L Jeffrey
LJ
Medeiros
Carlos E
CE
Bueso-Ramos
D059786:Abnormal Karyotype; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001752:Blast Crisis; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D016313:Genes, abl; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D010677:Philadelphia Chromosome; D055815:Young Adult
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D016044:Fusion Proteins, bcr-abl