CD34-positive acute promyelocytic leukemia is associated with leukocytosis, microgranular/hypogranular morphology, expression of CD2 and bcr3 isoform

Acute promyelocytic leukemia (APL) has a favorable prognosis. Current therapy includes chemotherapy used in combination with all-trans-retinoic acid (ATRA). Although the differentiating effects of ATRA on promyelocytes have been well established, in vitro studies have shown that less-differentiated APL blasts (CD34+) demonstrate a variable responsiveness to ATRA. To assess the clinical relevance of this finding, we analyzed a cohort of 38 patients with t(15;17) and/or PML-RAR APL to determine the incidence and laboratory features of CD34+ APL. Thirty-two percent (12/38) of cases were CD34+. There was a difference in WBC at presentation between CD34+ and CD34- cases (34.6 ± 9.2, mean ± standard error vs. 5.4 ± 2.0, P = 0.009). Patients with CD34+ APL demonstrated a micro/hypogranular phenotype (75%) (P = 0.001), coexpression of CD2+ (83%) (P = 0.001), and the bcr3 isoform (100%) (P = 0.017). In contrast, CD34- cases demonstrated hypergranular morphology (65%), CD2+ (15%), and the bcr1 isoform (50%). A high presenting WBC count (\G10 × 109/L) was associated with an inferior overall survival (Log rank = 0.0047). Patients with CD34+ APL demonstrated an incidence of early mortality of 50%. Despite a marked correlation between CD34 positivity and increased WBC count, overall survival of CD34+ and CD34- cases did not differ significantly in our small cohort. Immunophenotypic analysis for CD34 expression should be included in future large APL trials to determine if detection of CD34+ blasts represents an independent adverse prognostic factor.