Surface antigens analysis reveals significant expression of candidate targets for immunotherapy in adult acute lymphoid leukemia

In the last decade the use of intensive chemotherapy and eventually stem cell transplant has provided significant progress in the outcome of adult patients with acute lymphoid leukemia (ALL) [1]. However, their prognosis remains disappointing in most cases [1]. Thus, new therapies are warranted [1]. ALL blast cells express a variety of lineage-specific antigens [2], which are used for the establishment of diagnosis and definition of immunologic subtypes [3]. Surface and intracellular antigens may, however, also serve as targets for treatment with monoclonal antibodies (MoAbs). Antibody therapy is an alternative and attractive treatment approach in ALL since it is targeted, subtype specific, and, compared to chemotherapy, has different mechanisms of action and side effects [4]. Antibody therapy may therefore be offered particularly to patients in whom the intensification of chemotherapy is impossible, and may act on leukemic clones which are resistant to cytostatic drugs. In addition, the synergistic effects of antibody therapy and chemotherapy can be utilized. MoAbs can be administered (1) in unconjugated form, (2) conjugated to chemotherapeutic agents or immunotoxins, which are carried to the target cell by the antibody, or (3) conjugated to radioactive molecules, which deliver radiation selectively to malignant cells [5]. There is some evidence that the activity of antibodies depends on the degree of antigen expression on the cell surface. Thus, a prerequisite for MoAb therapy is generally the presence of the target antigen on at least 20–30% of neoplastic cells. If the incidence of antigen-positive cells is higher, the chance of clinical response is theoretically higher as well. To date, only a few data are available regarding the expression of potential surface targets in different ALL subtypes, including a limited number of patients who are BCR/ABL1þ [6,7]. In this study, we aimed to assess the frequency of expression of CD19, CD20, CD22, CD33, and CD52 in different ALL subtypes, for which MoAbs have been developed for immunotherapy (blinatumomab, rituximab, epratuzumab, inotuzumab ozogamicin, gemtuzumab ozogamicin, and alemtuzumab). We studied 104 consecutive adult cases of ALL diagnosed at the Hematopathology and Hematology units of Bologna and Udine universities. Their median age was 40 (range, 16–75) years. According to the World Health Organization (WHO) classification [3,8,9], our series consisted of T-lymphoblastic leukemia/lymphoma (n1⁄4 14), B-lymphoblastic leukemia/lymphoma, not otherwise specified (ALL/NOS; n1⁄4 48), and B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities (n1⁄4 42). The latter included cases of BCR/ABL1þ (n1⁄4 34), E2A/ PBX1þ (n1⁄4 3), and MLL rearrangement (n1⁄4 5). Samples of bone marrow harvested from each patient were collected into ethylenediaminetetraacetic