Flow Cytometry Rapidly Identifies All Acute Promyelocytic Leukemias With High Specificity Independent of Underlying Cytogenetic Abnormalities

Abstract

Acute promyelocytic leukemia (APL) is a highly aggressive disease requiring prompt diagnosis and specific early intervention. Immunophenotyping by flow cytometry (FCM) facilitates a rapid diagnosis, but commonly used criteria are neither sufficiently sensitive nor specific. With an antibody panel for diagnostic screening in routine practice, we found all 149 APL cases in this study exhibited a unique immunophenotypic profile, ie, a characteristic CD11b- myeloid population and absent CD11c expression in all myeloid populations; 96.6% of cases also lacked HLA-DR expression. These distinctive features allowed recognition of all unusual cases phenotypically resembling the regular myeloblasts (CD34+/HLA-DR+) or granulocytes (CD117-/CD34-/HLA-DR-). FCM effectively identified all 19 APL cases with variant translocations, including cases with a normal karyotype due to a cryptic submicroscopic t(15;17)(q22;q21), t(11;17)(q23;q21) that escaped the detection by fluorescence in situ hybridization for t(15;17) and der(15)ider(17)(q10) that lacked a simple reciprocal t(15;17). When APL-associated profiles were validated against 107 AML cases of non-APL subtypes, including 51 HLA-DR- cases, the diagnostic specificity and positive predictive value were 98%. FCM effectively provides independent detection of APL during diagnostic workup and harmonizes with the subsequent molecular cytogenetic diagnosis.