TY - JOUR
T1 - Acute myeloid leukemia with t(9;11)(p21-22;q23)
T2 - Common properties of dysregulated Ras pathway signaling and genomic progression characterize de novo and therapy-related cases
AU - Chandra, Pranil
AU - Luthra, Rajyalakshmi
AU - Zuo, Zhuang
AU - Yao, Hui
AU - Ravandi-Kashani, Farhad
AU - Reddy, Neeli
AU - Garcia-Manero, Guillermo
AU - Kantarjian, Hagop M
AU - Jones, Dan
PY - 2010/5
Y1 - 2010/5
N2 - 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.
AB - 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.
KW - Let-7
KW - Leukemogenesis
KW - MicroRNA
KW - Mixed lineage leukemia (MLL)
KW - Ras signaling
KW - Treatment effects
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UR - http://www.scopus.com/inward/citedby.url?scp=77951899709&partnerID=8YFLogxK
U2 - 10.1309/AJCPGII1TT4NYOGI
DO - 10.1309/AJCPGII1TT4NYOGI
M3 - Article
C2 - 20395514
AN - SCOPUS:77951899709
SN - 0002-9173
VL - 133
SP - 686
EP - 693
JO - American journal of clinical pathology
JF - American journal of clinical pathology
IS - 5
ER -