HDM4 (HDMX) is widely expressed in adult pre-B acute lymphoblastic leukemia and is a potential therapeutic target

Xin Han, Guillermo Garcia-Manero, Timothy J. McDonnell, Guillermina Lozano, L. Jeffrey Medeiros, Lianchun Xiao, Gary Rosner, Martin Nguyen, Michael Fernandez, Yasmine A. Valentin-Vega, Juan Barboza, Daniel M. Jones, Georgios Z. Rassidakis, Hagop M. Kantarjian, Carlos E. Bueso-Ramos

Research output: Contribution to journalArticle

Abstract

Human homolog of murine double minute 2 (HDM2) and HDM4 (or HDMX) are negative regulators of p53. HDM4 has not been assessed in precursor B (pre-B) lymphoblastic leukemia (ALL). We examined bone marrow samples obtained at time of diagnosis from 55 adults with pre-B ALL. A tissue microarray composed of 2 cores per specimen was constructed and immunohistochemical techniques were used to assess HDM4, HDM2, p53, and p21. HDM4 was expressed in 39 of 49 (80%) cases. HDM2 was expressed in 14 of 54 (26%). All HDM2-positive cases were also positive for HDM4 (P<0.05). We confirmed expression of HDM4 and HDM4 variants by Western blotting and sequencing of reverse transcription-polymerase chain reaction products in a subset of ALL tumors. Results were correlated with the presence of the Philadelphia chromosome (Ph). p53 (P<0.05) and p21 (P<0.001) were expressed significantly more often in Ph+ pre-B ALL. HDM4 and HDM2 showed no correlation with Ph status. HDM4 expression in most cases of adult pre-B ALL suggests that HDM4 is a potential therapeutic target.

Original languageEnglish (US)
Pages (from-to)54-62
Number of pages9
JournalModern Pathology
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

Keywords

  • HDM2
  • HDMX
  • Mdm4
  • Precursor B lymphoblastic leukemia
  • p21
  • p53

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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  • Cite this

    Han, X., Garcia-Manero, G., McDonnell, T. J., Lozano, G., Medeiros, L. J., Xiao, L., Rosner, G., Nguyen, M., Fernandez, M., Valentin-Vega, Y. A., Barboza, J., Jones, D. M., Rassidakis, G. Z., Kantarjian, H. M., & Bueso-Ramos, C. E. (2007). HDM4 (HDMX) is widely expressed in adult pre-B acute lymphoblastic leukemia and is a potential therapeutic target. Modern Pathology, 20(1), 54-62. https://doi.org/10.1038/modpathol.3800727