Acute myeloid leukemia with t(9;11)(p21-22;q23): common properties of dysregulated ras pathway signaling and genomic progression characterize de novo and therapy-related cases.
We compared pathogenetic features of 32 de novo and 29 therapy-related (t) t(9;11)(p21-22;q23)/MLLT3-MLL acute myeloid leukemia (AML) cases to identify progression factors and to assess whether distinction between these manifestations is warranted. MLLT3-MLL rearrangement was commonly the sole karyotypic abnormality at diagnosis, with many secondary chromosomal changes emerging at relapse in both subgroups. Ras point mutations were common in both groups (overall, 18/50 [36%]) and associated with monocytic phenotype and aneuploid progression. Expression patterns of 675 microRNAs profiled in 7 cases were also similar, with let-7 species linked to Ras down-modulation expressed at low levels. Outcome for both groups was poor (relapsed or refractory in 49/61 [80%] cases); however, patients with t-AML were generally older and female, with worse outcome (P = .03), likely secondary to t-AML mostly arising in patients with breast cancer following topoisomerase inhibitor-containing chemotherapy. Ras activation seems to complement the MLLT3-MLL oncogene in transformation with features of de novo and t-AML with MLLT3-MLL being similar.
Chandra
Pranil
P
Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Luthra
Rajyalakshmi
R
Zuo
Zhuang
Z
Yao
Hui
H
Ravandi
Farhad
F
Reddy
Neeli
N
Garcia-Manero
Guillermo
G
Kantarjian
Hagop
H
Jones
Dan
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11; D002899:Chromosomes, Human, Pair 9; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D017354:Point Mutation; D015398:Signal Transduction; D015996:Survival Rate; D013781:Texas / Q000453:epidemiology; D014178:Translocation, Genetic; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
C497422:KMT2A protein, human; C489901:MLLT3 protein, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D018631:ras Proteins