DOI QR코드

DOI QR Code

Aberrant Expression of HOXA5 and HOXA9 in AML

  • Zhao, Peng (Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University) ;
  • Tan, Li (Department of Hematology, the First Affiliated Hospital of Guangzhou Medical University) ;
  • Ruan, Jian (Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University) ;
  • Wei, Xiao-Ping (Department of Hematology, the First Affiliated Hospital of Guangzhou Medical University) ;
  • Zheng, Yi (Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University) ;
  • Zheng, Li-Xia (Department of Hematology, the First Affiliated Hospital of Guangzhou Medical University) ;
  • Jiang, Wei-Qin (Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University) ;
  • Fang, Wei-Jia (Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University)
  • Published : 2015.05.18

Abstract

Background: Aberrant expression of HOX gene expression has been observed in cancer. The purpose of this study was to investigate the alteration of HOXA5 and HOXA9 expression and their clinical significance in acute meloid leukemia (AML). Materials and Methods: The expression of HOXA5 and HOXA9 genes of bone marrow samples from 75 newly diagnosed AML patients and 22 healthy controls for comparison were examined by Real-time quantitative PCR (RQ-PCR) assay. Statistical analysis was conducted to evaluate HOXA5 and HOXA9 expression as possible biomarkers for AML. Results: The results showed that the complete remission rate (52.6%) of the patients who highly expressed HOXA5 and HOXA9 was significantly lower than that (88.9%) in patients who lowly express the genes (P=0.015). Spearmann correlation coefficients indicated that the expression levels for HOXA5 and HOXA9 genes were highly interrelated (r=0.657, P<0.001). Meanwhile, we detected significant correlations between HOXA9 expression and age in this limited set of patients (P=0.009). Conclusions: The results suggest a prognostic impact of increased expression of HOXA5 and HOXA9 in AML patients.

Keywords

References

  1. Abramovich C, Humphries RK (2005). Hox regulation of normal and leukemic hematopoietic stem cells. Curr Opin Hematol, 12, 210-16. https://doi.org/10.1097/01.moh.0000160737.52349.aa
  2. Arocho A, Chen B, Ladanyi M, Pan Q (2006). Validation of the 2-DeltaDeltaCt calculation as an alternate method of dataanalysis for quantitative PCR of BCR-ABL P210 transcripts. Diagn Mol Pathol, 15, 56-61. https://doi.org/10.1097/00019606-200603000-00009
  3. Bennett JM, Catovsky D, Daniel MT, Flandrin G, et al (1985). Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. Ann Intern Med, 103, 620-5. https://doi.org/10.7326/0003-4819-103-4-620
  4. Borrow J, Shearman AM, Stanton VP Jr, et al (1996). The t (7;11) (p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporinNUP98 and class I homeoprotein HOXA9. Nat Genet, 12, 159-67. https://doi.org/10.1038/ng0296-159
  5. Boucherat O, Guillou F, Aubin J, et al (2009). Hoxa5: a master gene with multifaceted roles. Med Sci (Paris), 25, 77-82. https://doi.org/10.1051/medsci/200925177
  6. Cancer Genome Atlas Research Network (2013). Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med, 368, 2059-74. https://doi.org/10.1056/NEJMoa1301689
  7. Cillo C, Cantile M, Faiella A, et al (2001). Homeobox genes in normal and malignant cells. J Cell Physiol, 188, 161-9. https://doi.org/10.1002/jcp.1115
  8. Cooks GM, Fuller J, Petersen D, et al (1999). Constitutive HOXA5 expression inhibits erythropoiesis and increases myelopoiesis from humanhematopoietic progenitors. Blood, 94, 519-28.
  9. Drabkin HA, Parsy C, Ferguson K, et al (2002). Quantitative HOX expression in chromosomally defined subsets of acute myelogenousleukemia. Leukemia, 16, 186-95. https://doi.org/10.1038/sj.leu.2402354
  10. Estey E, Dohner H (2006). Acute myeloid leukaemia. Lancet, 368, 1894-90. https://doi.org/10.1016/S0140-6736(06)69780-8
  11. Fuller JF, McAdara J, Yaron Y, et al (1999). Characterization of HOX gene expression during myelopoiesis: role of HOX A5 in lineage commitment and maturation. Blood, 93, 3391-400.
  12. Golub TR, Slonim DK, Tamayo P, et al (1999). Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science, 286, 531-7. https://doi.org/10.1126/science.286.5439.531
  13. Gonzalez Garcia JR, Meza-Espinoza JP (2006). Use of the International System for Human Cytogenetic Nomenclature (ISCN). Blood, 108, 3952-3. https://doi.org/10.1182/blood-2006-06-031351
  14. Hou HA, Lin CC, Chou WC, et al (2014). Integration of cytogenetic and molecular alterations in risk stratification of 318 patients with denovo non-M3 acute myeloid leukemia. Leukemia, 28, 50-8. https://doi.org/10.1038/leu.2013.236
  15. Kumar A, Vashist M, Rathee R (2014). Maternal factors and risk of childhood leukemia. Asian Pac J Cancer Prev, 15, 781-4. https://doi.org/10.7314/APJCP.2014.15.2.781
  16. Li Y, Lin J, Yang J, Qian J, et al (2013). Overexpressed let-7a-3 is associated with poor outcome in acute myeloid leukemia. Leuk Res, 37, 1642-7. https://doi.org/10.1016/j.leukres.2013.09.022
  17. Nakamura T, Largaespada DA, Lee MP, Johnson LA et al (1996). Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t (7;11) (p15;p15) in human myeloid leukaemia. Nat Genet, 12, 154-8. https://doi.org/10.1038/ng0296-154
  18. Nakamura T, Yamazaki Y, Hatano Y, et al (1999). NUP98 is fused to PMX1 homeobox gene in human acute myelogenous leukemia withchromosome translocation t (1;11) (q23;p15). Blood, 94, 741-7.
  19. Sabattini E, Bacci F, Sagramoso C, et al (2008). WHO classification of tumours of haematopoietic and lymphoid tissues in 2008: an overview. Pathologica, 102, 83-8.
  20. Shahab S, Shamsi TS, Ahmed N (2013). Prognostic involvement of nucleophosmin mutations in acute myeloid leaukemia. Asian Pac J Cancer Prev, 14, 5615-20. https://doi.org/10.7314/APJCP.2013.14.10.5615
  21. Spencer DH, Young MA, Lamprecht TL, et al (2015). Epigenomic analysis of the HOX gene loci reveals mechanisms that may control canonical expression patterns in AML and normal hematopoietic cells.Leukemia. 2015 Jan 20.
  22. Thorsteinsdottir U, Kroon E, Jerome L, et al (2001). Defining roles for HOX and MEIS1 genes in induction of acute myeloid leukemia. Mol Cell Biol, 21, 224-34. https://doi.org/10.1128/MCB.21.1.224-234.2001
  23. van Oostveen J, Bijl J, Raaphorst F, et al (1999). The role of homeobox genes in normal hematopoiesis and hematological malignancies. Leukemia, 13, 1675-90. https://doi.org/10.1038/sj.leu.2401562

Cited by

  1. RNA and protein expression of herpesvirus entry mediator (HVEM) is associated with molecular markers, immunity-related pathways and relapse-free survival of patients with AML vol.64, pp.12, 2015, https://doi.org/10.1007/s00262-015-1755-8
  2. HOXA3 promotes tumor growth of human colon cancer through activating EGFR/Ras/Raf/MEK/ERK signaling pathway vol.119, pp.3, 2018, https://doi.org/10.1002/jcb.26461
  3. Silencing of HMGA2 reverses retardance of cell differentiation in human myeloid leukaemia vol.118, pp.3, 2018, https://doi.org/10.1038/bjc.2017.403
  4. Therapeutic potential of GSK-J4, a histone demethylase KDM6B/JMJD3 inhibitor, for acute myeloid leukemia vol.144, pp.6, 2018, https://doi.org/10.1007/s00432-018-2631-7