TY - JOUR
T1 - HDM4 (HDMX) is widely expressed in adult pre-B acute lymphoblastic leukemia and is a potential therapeutic target
AU - Han, Xin
AU - Garcia-Manero, Guillermo
AU - McDonnell, Timothy J.
AU - Lozano, Guillermina
AU - Medeiros, L. Jeffrey
AU - Xiao, Lianchun
AU - Rosner, Gary
AU - Nguyen, Martin
AU - Fernandez, Michael
AU - Valentin-Vega, Yasmine A.
AU - Barboza, Juan
AU - Jones, Daniel M.
AU - Rassidakis, Georgios Z.
AU - Kantarjian, Hagop M.
AU - Bueso-Ramos, Carlos E.
N1 - Funding Information:
Parts of this work were presented at the US and Canadian Academy of Pathology Annual Meeting, San Antonio, TX, USA, February 26–March 4, 2005. Dr X Han is the recipient of the Research Fellowship awarded by the Division of Pathology and Laboratory Medicine, The University of Texas, MD Anderson Cancer Center. We are grateful to Donald R Norwood, LaKisha Rodgers, and Ana Martinez for help in preparation of the manuscript and to Remigio Lopez, Vilmos Thomazy, and Shawn Bris-bay for excellent technical support.
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
KW - HDM2
KW - HDMX
KW - Mdm4
KW - Precursor B lymphoblastic leukemia
KW - p21
KW - p53
UR - https://www.scopus.com/pages/publications/33845695691
U2 - 10.1038/modpathol.3800727
DO - 10.1038/modpathol.3800727
M3 - Article
C2 - 17143258
AN - SCOPUS:33845695691
SN - 0893-3952
VL - 20
SP - 54
EP - 62
JO - Modern Pathology
JF - Modern Pathology
IS - 1
ER -