TY - JOUR
T1 - Analysis of Aurora kinase A expression in CD34+ blast cells isolated from patients with myelodysplastic syndromes and acute myeloid leukemia
AU - Ye, Dongjiu
AU - Garcia-Manero, Guillermo
AU - Kantarjian, Hagop M.
AU - Xiao, Lianchun
AU - Vadhan, Saroj
AU - Fernandez, Michael H.
AU - Nguyen, Martin H.
AU - Medeiros, L. Jeffrey
AU - Bueso-Ramos, Carlos E.
N1 - Funding Information:
Acknowledgments Parts of this work were presented at the US and Canadian Academy of Pathology 97th Annual Meeting, Denver, CO, USA, March 1–7, 2008. Dr. Dongjiu Ye is the recipient of the Research Fellowship awarded by the Division of Pathology and Laboratory Medicine, The University of Texas, M. D. Anderson Cancer Center. We thank Kathryn Hale for her assistance in editing this manuscript and LaKisha Rodgers for her assistance in formatting the figures and the manuscript.
PY - 2009
Y1 - 2009
N2 - Aurora kinase A, also known as aurora A, is a serine/threonine kinase that plays critical roles in mitosis entry, chromosome alignment, segregation, and cytokinesis. Overexpression of aurora A has been observed in many solid tumors and some hematopoietic neoplasms, but little is known about its expression in myeloid diseases. Because cytogenetic abnormalities play an essential role in the pathogenesis of myeloid malignancies, we hypothesized that aurora A deregulation may be involved in myelodysplastic syndromes and acute myeloid leukemia and contribute to the chromosomal instability observed in these diseases. We assessed aurora A mRNA levels in CD34+ bone marrow blasts from nine patients with acute myeloid leukemia, 20 patients with myelodysplastic syndromes, and five normal patients serving as controls. CD34+ blasts were isolated from bone marrow aspirate specimens using magnetic activated cell separation technology. RNA was extracted from purified CD34+ cells, and quantitative realtime reverse transcriptase polymerase chain reaction for aurora A was performed. Immunocytochemical analyses for total aurora A, phosphorylated aurora A, Ki-67, and activated caspase 3 were performed on cytospin slides made from purified CD34+ cells in myelodysplastic syndrome patients using standard methods. Aurora A mRNA and protein levels were correlated, as was aurora A mRNA level, with blast counts, cytogenetic abnormalities, and International Prognostic Scoring System score. We found that CD34+ cells in myelodysplastic syndromes and acute myeloid leukemia expressed aurora A at significantly higher levels (P=0.01 and P=0.01, respectively) than normal CD34+ cells. Aurora A mRNA levels correlated with total and phosphorylated protein levels (P=0.0002 and P=0.02, respectively). No significant correlation was found between aurora A mRNA level and blast count, blast viability, cytogenetic abnormalities, or the International Prognostic Scoring System score in patients with myelodysplastic syndromes. We conclude that aurora A is upregulated in CD34+ blasts from myeloid neoplasms.
AB - Aurora kinase A, also known as aurora A, is a serine/threonine kinase that plays critical roles in mitosis entry, chromosome alignment, segregation, and cytokinesis. Overexpression of aurora A has been observed in many solid tumors and some hematopoietic neoplasms, but little is known about its expression in myeloid diseases. Because cytogenetic abnormalities play an essential role in the pathogenesis of myeloid malignancies, we hypothesized that aurora A deregulation may be involved in myelodysplastic syndromes and acute myeloid leukemia and contribute to the chromosomal instability observed in these diseases. We assessed aurora A mRNA levels in CD34+ bone marrow blasts from nine patients with acute myeloid leukemia, 20 patients with myelodysplastic syndromes, and five normal patients serving as controls. CD34+ blasts were isolated from bone marrow aspirate specimens using magnetic activated cell separation technology. RNA was extracted from purified CD34+ cells, and quantitative realtime reverse transcriptase polymerase chain reaction for aurora A was performed. Immunocytochemical analyses for total aurora A, phosphorylated aurora A, Ki-67, and activated caspase 3 were performed on cytospin slides made from purified CD34+ cells in myelodysplastic syndrome patients using standard methods. Aurora A mRNA and protein levels were correlated, as was aurora A mRNA level, with blast counts, cytogenetic abnormalities, and International Prognostic Scoring System score. We found that CD34+ cells in myelodysplastic syndromes and acute myeloid leukemia expressed aurora A at significantly higher levels (P=0.01 and P=0.01, respectively) than normal CD34+ cells. Aurora A mRNA levels correlated with total and phosphorylated protein levels (P=0.0002 and P=0.02, respectively). No significant correlation was found between aurora A mRNA level and blast count, blast viability, cytogenetic abnormalities, or the International Prognostic Scoring System score in patients with myelodysplastic syndromes. We conclude that aurora A is upregulated in CD34+ blasts from myeloid neoplasms.
KW - Acute myeloid leukemia
KW - Aurora A
KW - Myelodysplastic syndromes
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U2 - 10.1007/s12308-008-0019-3
DO - 10.1007/s12308-008-0019-3
M3 - Article
C2 - 19669217
AN - SCOPUS:77956527688
SN - 1865-5785
VL - 2
SP - 2
EP - 8
JO - Journal of Hematopathology
JF - Journal of Hematopathology
IS - 1
ER -