TY - JOUR
T1 - Comparative analysis of genes regulated in acute myelomonocytic leukemia with and without inv(16)(p13q22) using microarray techniques, real-time PCR, immunohistochemistry, and flow cytometry immunophenotyping
AU - Sun, Xiaoping
AU - Zhang, Wei
AU - Ramdas, Latha
AU - Stivers, David N.
AU - Jones, Daniel M.
AU - Kantarjian, Hagop M.
AU - Estey, Elihu H.
AU - Vadhan-Raj, Saroj
AU - Medeiros, L. Jeffrey
AU - Bueso-Ramos, Carlos E.
N1 - Funding Information:
This project was supported by a fellow research funding award from the Division of Pathology and Laboratory Medicine at MD Anderson to XS, an Olla Stribling fund to CBR, National Cancer Institute Cancer Center Support Grant 5P30 CA016672-28, the Tobacco Settlement Fund to MD Anderson as appropriated by the Texas legislature, and funds from the Kadoorie Foundation to the Genomics Facility. We thank Martin H Nguyen and Ellen Taylor for their excellent technical assistance. We thank Ann Sutton for her editorial suggestions. We also thank Ana M Martinez for her secretarial support.
PY - 2007/8/11
Y1 - 2007/8/11
N2 - Acute myeloid leukemia with inv(16)(p13q22), also known as M4Eo, is a distinct type of leukemia with characteristic clinicopathologic and cytogenetic features. Patients with M4Eo have monocytosis, high blast counts, and abnormal bone marrow eosinophils that contain large basophilic granules. The inv(16)(p13q22) or, less commonly, the t(16;16)(p13;q22) causes fusion of the CBFβ gene at 16q22 and the MYH11 gene at 16p13, creating the novel chimeric protein CBFβ-MYH11. To understand the underlying molecular mechanisms unique to M4Eo biology, we determined the gene expression profile of M4Eo cases by using cDNA and long oligonucleotide microarrays. Cases of acute myelomonocytic leukemia without CBFβ-MYH11 (M4) acted as our control. We found that in the gene expression profile of M4Eo, NF-κB activators and inhibitors were upregulated and downregulated, respectively, suggesting that the NF-κB signaling pathway is activated at a higher level in M4Eo than in acute myelomonocytic leukemia M4. In addition, the gene expression profile of M4Eo indicates high cell proliferation and low apoptosis. We used real-time PCR, immunohistochemistry, and flow cytometry immunophenotyping to confirm some of our microarray data. These findings most likely represent the functional consequences of the abnormal chimeric protein CBFβ-MYH11, which is unique to this disease, and suggest that NF-κB is a potential therapeutic target for treating M4Eo patients.
AB - Acute myeloid leukemia with inv(16)(p13q22), also known as M4Eo, is a distinct type of leukemia with characteristic clinicopathologic and cytogenetic features. Patients with M4Eo have monocytosis, high blast counts, and abnormal bone marrow eosinophils that contain large basophilic granules. The inv(16)(p13q22) or, less commonly, the t(16;16)(p13;q22) causes fusion of the CBFβ gene at 16q22 and the MYH11 gene at 16p13, creating the novel chimeric protein CBFβ-MYH11. To understand the underlying molecular mechanisms unique to M4Eo biology, we determined the gene expression profile of M4Eo cases by using cDNA and long oligonucleotide microarrays. Cases of acute myelomonocytic leukemia without CBFβ-MYH11 (M4) acted as our control. We found that in the gene expression profile of M4Eo, NF-κB activators and inhibitors were upregulated and downregulated, respectively, suggesting that the NF-κB signaling pathway is activated at a higher level in M4Eo than in acute myelomonocytic leukemia M4. In addition, the gene expression profile of M4Eo indicates high cell proliferation and low apoptosis. We used real-time PCR, immunohistochemistry, and flow cytometry immunophenotyping to confirm some of our microarray data. These findings most likely represent the functional consequences of the abnormal chimeric protein CBFβ-MYH11, which is unique to this disease, and suggest that NF-κB is a potential therapeutic target for treating M4Eo patients.
KW - CBFβ-MYH11
KW - Gene expression
KW - Leukemia
KW - M4Eo
KW - NF-κB
KW - inv(16)
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U2 - 10.1038/modpathol.3800829
DO - 10.1038/modpathol.3800829
M3 - Article
C2 - 17571080
AN - SCOPUS:34447579042
SN - 0893-3952
VL - 20
SP - 811
EP - 820
JO - Modern Pathology
JF - Modern Pathology
IS - 8
ER -