DNA damage response (DNADR) recognition and repair (DDR) pathways affect
carcinogenesis and
therapy responsiveness in
cancers, including
leukemia. We measured
protein expression levels of 16 DNADR and
DDR proteins using the Reverse Phase
Protein Array methodology in acute myeloid (AML) (n = 1310), T-cell
acute lymphoblastic leukemia (
T-ALL) (n = 361) and
chronic lymphocytic leukemia (CLL) (n = 795) cases. Clustering analysis identified five
protein expression clusters; three were unique compared to normal CD34+ cells. Individual
protein expression differed by disease for 14/16
proteins, with five highest in CLL and nine in
T-ALL, and by age in
T-ALL and AML (six and eleven
proteins, respectively), but not CLL (n = 0). Most (96%) of the CLL cases clustered in one cluster; the other 4% were characterized by higher frequencies of
deletion 13q and 17p, and fared poorly (p < 0.001).
T-ALL predominated in C1 and AML in C5, but both occurred in all four acute-dominated clusters.
Protein clusters showed similar implications for survival and remission duration in pediatric and adult
T-ALL and AML populations, with C5 doing best in all. In summary, DNADR and DDR
protein expression was abnormal in
leukemia and formed recurrent clusters that were shared across the
leukemias with shared prognostic implications across diseases, and individual
proteins showed age- and disease-related differences.