CD22 expression in acute myeloid leukemia: close correlation with interleukin-2 receptor α-chain (CD25) expression and poor prognosis

Acute myeloid leukemia (AML) is a biologically and clinically heterogenous disease. Although similar chemotherapeutic regimens were used for the majority of patients with AML until recently, newer treatment approaches are now developing due to progress in the understanding of the pathophysiology of AML [1]. Lymphoid associated antigen expression is closely related to the pathological status of patients with AML. Several investigators have demonstrated biological and clinical properties of AML expressing T-lymphoid antigens such as CD2 [2], CD4 [3] and CD7 [4]. As for B-lymphoid antigens, although CD19 expression in AML has been studied in detail [5], little data is available about CD22 expression in AML. In this study, we analyzed the expression of CD22 in a large population of adult patients with previously untreated, de novo AML, and determined the cellular characteristics and clinical features of such AML: response to chemotherapy and overall survival (OS) were evaluated in patients receiving intensive chemotherapy. Details of the study design and methods are available in Supplementary Materials. CD22 was observed in 10 of the 404 patients (2.5%) with AML. The expression range and median of CD22 positivity among its positive cases were 15–86% and 24%, respectively. FAB subtypes of 10 patients were as follows: 6 M1, 3 M4, and 1 M5. Morphological basophilic and mast cell features were not observed in leukemic cells from any patient with this AML. All 10 cases expressed CD13, CD34 and HLA-DR. CD117 and CD123 were highly expressed in 4 patients examined (Supplementary Table 1). These cases were characterized by the expression of various lymphoid associated antigens such as CD10, CD19, CD20, CD21, CD2, CD4, CD5, CD7, CD25, CD56, and/or TdT. Of the 4 patients analyzed for immune-genotypes, IgH and TcRc gene rearrangements were simultaneously observed in 1 (Table 1). Cytogenetically, of the 8 patients examined del (5) and 7 were displayed in 1 patient each and t(9;22) (Ph1) in 2 (Supplementary Table 2). FLT3-ITD was analyzed in 24 patients and was positive in 10 out of the 23 patients with CD22 AML, whereas it was negative in only 1 CD22 AML patient examined. Of note is that CD22 patients more frequently expressed CD34, CD19, CD2, CD25, and Ph1 abnormality, and had more highly expression levels of CD123 than CD22 patients (Supplementary Table 3). Interestingly, the most common lymphoid associated antigen found on CD22 cases was the CD25 antigen: CD22 cases were more apt to display CD25 than CD22 cases [7/8 (87.5%) vs. 38/384 (9.9%), p< 0.001]. CD25 (IL-2Ra) has been reported as a dismal prognostic marker of AML [6] and is described to promote the growth of CD25 AML cells in an IL-2 independent manner [7]. Even in this cohort, patients with CD25 AML had a lower complete remission (CR) rate [18/34 (52.9%) vs. 226/308 (73.4%), p1⁄4 0.016] and an inferior OS compared to those with CD25 AML (Supplementary Figure 1). Meanwhile, CD22 AML cases also showed a lower CR rate [1/7 (14.3%) vs. 247/343 (72.0%), p1⁄4 0.003] and a shorter OS than CD22 AML cases (Figure 1). In addition, white blood cell (WBC) counts were higher in CD22 AML than in the other subtypes of AML (Supplementary Table 4). These clinical characteristics might be closely associated with the concomitant CD25 expression, and therapeutic strategies directed at CD25 could be opted for the treatment of CD22 AML. The incidence of CD22 expression in AML is in line with most previous reports, demonstrating the rare expression (<7%) [8,9]. On the contrary, Saito et al. [10]. described that CD22 was frequently observed in AML-M0 and secondary AML (11/64 AML patients, 17.2%), and these cases consisted of basophil-related leukemias expressing CD13 and CD25 simultaneously. However, our AML cases appeared different AML from those mentioned in the study by Saito et al. [10] because we observed