AML1-ETO9a is correlated with C-KIT overexpression/mutations and indicates poor disease outcome in t(8;21) acute myeloid leukemia-M2

作者: B Jiao , CF Wu , Y Liang , HM Chen , SM Xiong

DOI: 10.1038/LEU.2009.104

关键词:

摘要: AML1-ETO fusion gene is generated from chromosomal translocation t(8;21) mainly in acute myeloid leukemia M2 subtype (AML-M2). Its spliced variant transcript, AML1-ETO9a, rapidly induces murine model. To evaluate its clinical significance, AML1-ETO9a expression was assessed 118 patients with AML-M2, using qualitative and nested quantitative reverse transcriptase (RT)-PCR methods. These cases were accordingly divided into the AML1-ETO9a-H group (n=86, positive for RT-PCR, higher level of by RT-PCR) AML1-ETO9a-L (n=32, negative lower but still detectable RT-PCR). C-KIT significantly increased group, as compared group. Of 36 harboring mutations, 32 overexpressed (P=0.0209). Clinically, exhibited elevated white blood cells count, less bone marrow aberrant myelocytes, CD56 decreased CD19 (P=0.0451, P=0.0479, P=0.0149 P=0.0298, respectively). Moreover, overexpression related to short event-free overall survival time (P=0.0072 P=0.0076, Taken together, these data suggest that correlated overexpression/mutations indicates poor disease outcome AML-M2.

参考文章(33)
Alessandro Beghini, Paolo Peterlongo, Carla B. Ripamonti, Lidia Larizza, Roberto Cairoli, Enrica Morra, Cristina Mecucci, C-kit mutations in core binding factor leukemias. Blood. ,vol. 95, pp. 726- 728 ,(2000) , 10.1182/BLOOD.V95.2.726
Dao-Pei Lu, Jian-Feng Fu, Bin Jiang, De-Bing Wang, Jing-Ying Qiu, Hong-Xia Shi, Xi-Jing Lu, Studies of treatment strategy and prognosis on acute myeloid leukemia with chromosome 8 and 21 translocation Chinese Journal of Hematology. ,vol. 26, pp. 481- ,(2005)
Kristina L. Rhoades, Christopher J. Hetherington, Nari Harakawa, Donald A. Yergeau, Liming Zhou, Li-Qin Liu, Marie-Terese Little, Daniel G. Tenen, Dong-Er Zhang, Analysis of the role of AML1-ETO in leukemogenesis, using an inducible transgenic mouse model Blood. ,vol. 96, pp. 2108- 2115 ,(2000) , 10.1182/BLOOD.V96.6.2108
John C. Byrd, Richard K. Dodge, Andrew Carroll, Maria R. Baer, Colin Edwards, Judith Stamberg, Mazin Qumsiyeh, Joseph O. Moore, Robert J. Mayer, Frederick Davey, Charles A. Schiffer, Clara D. Bloomfield, Patients With t(8;21)(q22;q22) and Acute Myeloid Leukemia Have Superior Failure-Free and Overall Survival When Repetitive Cycles of High-Dose Cytarabine Are Administered Journal of Clinical Oncology. ,vol. 17, pp. 3767- 3775 ,(1999) , 10.1200/JCO.1999.17.12.3767
Luke F. Peterson, Anita Boyapati, Eun-Young Ahn, Joseph R. Biggs, Akiko Joo Okumura, Miao-Chia Lo, Ming Yan, Dong-Er Zhang, Acute myeloid leukemia with the 8q22;21q22 translocation: secondary mutational events and alternative t(8;21) transcripts. Blood. ,vol. 110, pp. 799- 805 ,(2007) , 10.1182/BLOOD-2006-11-019265
F. Kuchenbauer, M. Feuring–Buske, C. Buske, AML1-ETO needs a partner: new insights into the pathogenesis of t(8;21) leukemia. Cell Cycle. ,vol. 4, pp. 1716- 1718 ,(2005) , 10.4161/CC.4.12.2256
John T. Reilly, Class III receptor tyrosine kinases: role in leukaemogenesis. British Journal of Haematology. ,vol. 116, pp. 744- 757 ,(2002) , 10.1046/J.0007-1048.2001.03294.X
Jitakshi De, Reza Zanjani, Michele Hibbard, Bruce H. Davis, Immunophenotypic Profile Predictive of KIT Activating Mutations in AML1-ETO Leukemia American Journal of Clinical Pathology. ,vol. 128, pp. 550- 557 ,(2007) , 10.1309/JVALJNL4ELQMD536
Susanne Schnittger, Tobias M. Kohl, Torsten Haferlach, Wolfgang Kern, Wolfgang Hiddemann, Karsten Spiekermann, Claudia Schoch, KIT-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival Blood. ,vol. 107, pp. 1791- 1799 ,(2006) , 10.1182/BLOOD-2005-04-1466
Chih-Cheng Chen, Jyh-Pyng Gau, Yuan-Bin Yu, Chang-Hsien Lu, Kuan-Der Lee, Jie-Yu You, Prognosis and treatment outcome in patients with acute myeloid leukemia with t(8;21)(q22;q22). Advances in Therapy. ,vol. 24, pp. 907- 920 ,(2007) , 10.1007/BF02849984