The homeobox gene CDX2 is aberrantly expressed and associated with an inferior prognosis in patients with acute lymphoblastic leukemia.
Molecular characterization of acute lymphoblastic leukemia (ALL) has greatly improved the ability to categorize and prognostify patients with this disease. In this study, we show that the proto-oncogene CDX2 is aberrantly expressed in the majority of cases with B-lineage ALL and T-ALL. High expression of CDX2 correlated significantly with the ALL subtype pro-B ALL, cALL, Ph(+) ALL and early T-ALL. Furthermore, high expression of CDX2 was associated with inferior overall survival and showed up as a novel and strong risk factor for ALL in bivariate analysis. Functional analyses showed that overexpression of Cdx2 in murine bone marrow progenitors perturbed genes involved in lymphoid development and that depletion of CDX2 in the human ALL cell line Nalm6 inhibited colony formation. These data indicate that aberrant CDX2 expression occurs frequently and has prognostic impact in adult patients with ALL.
Thoene
S
S
Department of Medicine III, Klinikum Grosshadern, Munich, Germany.
Rawat
V P S
VP
Heilmeier
B
B
Hoster
E
E
Metzeler
K H
KH
Herold
T
T
Hiddemann
W
W
Gökbuget
N
N
Hoelzer
D
D
Bohlander
S K
SK
Feuring-Buske
M
M
Buske
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D000071616:CDX2 Transcription Factor; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D015996:Survival Rate; D055815:Young Adult
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas