Evaluation of Novel Targets, Including CC-Chemokine Receptor 4, in Adult T-Cell Acute Lymphoblastic Leukemia/Lymphoma

Abstract

Context Unlike B-cell acute lymphoblastic leukemia/lymphoma (ALL/LBL), there have been few therapeutic advances in T-cell ALL/LBL, an aggressive ALL/LBL subtype. Objective To perform a focused tissue array study to elucidate tumor markers of therapeutic potential in T-ALL/LBL. Design Using immunohistochemistry, we evaluated expression of leukemic antigens of interest, specifically CC-Chemokine receptor 4 (CCR4), among others, on available remnant diagnostic material, including tumor tissue slides obtained from formalin-fixed, paraffin-embedded preserved tissues. Results Our analysis identified for the first time expression of CCR4 in T-ALL/LBL in 11 of 27 cases (40.7%) and confirmed common expression of BCL2, CD38, and CD47, as reported previously. We also identified the expression of CD123 in 4 of 26 cases (15.4%), whereas BCL6 and PDL1 were expressed in a small number of T-ALL/LBL cases. The potential novel target CCR4 was significantly more common in the Pre/Pro-T immunophenotypic (IP) subtype, 6 of 9 (66.7%, P = .011). No additional differences in clinical and epidemiologic variables were noted among positive or negative CCR4 cases. Conclusions These findings support preclinical and clinical testing of therapies targeting CCR4, CD47, BCL2, CD38, and CD123 in T-ALL/LBL, and may help guide the development of targeted clinical trials in T-cell ALL/LBL, a rare disease in urgent need of novel therapies.