Immunophenotype distinction between acute promyelocytic leukaemia and CD15− CD34− HLA‐DR− acute myeloid leukaemia with nucleophosmin mutations

Abstract

Acute promyelocytic leukaemia (APL) is a unique clinicobiologic entity that can be successfully treated with All-trans Retinoic Acid ATRA-based regimens. Some cases of acute myeloid leukaemia (AML) with nucleophosmin (NPM) mutations have an immunophenotype that is similar to APL. The objective of the study is to compare antigenic expression in a group of APL patients with that in AML patients with NPM mutations and an APL-like immunophenotype (CD15- CD34- HLA-DR-). A consecutive series of 40 APL and 12 NPM patients with an APL-like phenotype were included in the study. Immunophenotypic patterns were investigated by multiparametric flow cytometry. Promyelocytic leukaemia-retinoic acid receptor-α transcript type, NPM and FLT3 mutations were investigated using conventional methods. Statistically significant differences were found between APL and NPM-mutated AML in CD33, CD13, CD2 and CD110 reactivity. CD2 expression was absent in every patient with NPM-mutated AML. In addition, mean fluorescence intensity and the coefficient of variation (cv) of CD33 and CD13 showed statistical differences between the two groups for CD33 (p = 0.007) and a trend to significance for CD13 (p = 0.05). Furthermore, among 45 evaluable patients, CD110 expression statistically differentiates between the two groups: [2/33 (6%) in the APL group and 8/12 (66.6%) in the NPM-mutated AML (p = 0.014)]. However, these traits were subtle, raising the possibility of practical diagnostic challenges. In conclusion, CD110 and CD33 reactivity may be useful to distinguish APL from NPM-mutated AML with CD15, CD34 and HLA-DR negativity. Nevertheless, cytogenetic and molecular characterization is necessary to establish the accurate diagnosis of AML.

A novel flow cytometric method for enhancing acute promyelocytic leukemia screening by multidimensional dot-plots

“…More and more information has been accumulated over the past decade about this less common type of AML. It is characterized by normal karyotype, NPM1 mutation, and morphologically by “cup-like” blasts and M2 or M4 morphology as defined by FAB [17–20, 35, 36]. Despite these common denominators, morphology suggests that this is not a homogeneous subtype of AML, and yet, another advantage of our protocol is that it can detect various patterns among CD34-negative non-APL cases.…”

“…Their myeloblasts were CD117 positive, CD33 bright, and CD34 negative—this is the immunophenotype pattern most characteristic of APL. All patients in the non-APL group had normal karyotype and mutated NPM1 because this genetic feature is associated with CD34 negative myeloblasts [17–20]. The clinical and laboratory parameters of patients are summarized in Table 1.…”

Acute myeloid leukemia with mutated NPM1 mimics acute promyelocytic leukemia presentation

“…Most previous studies that focus on associations between immunophenotypic findings and genetic abnormalities in AML with APL‐like phenotype described de novo NPM1 ‐mutated AML cases 8,9 …”

“…Although uncommon, the “APL‐like” immunophenotype pattern has been reported in a subset of de novo AML with mutation of the nucleophosmin ( NPM1 ) gene 8,9 . NPM1 mutations are one of the most common genetic aberrations in AML.…”

Radar plots facilitate differential diagnosis of acute promyelocytic leukemia and NPM1+ acute myeloid leukemia by flow cytometry

“…The classical form of APL is usually easy to differentiate from NPM1 + AML by FCM due to characteristic high side scatter (SSC) (Macedo et al, 1995 ). However, detailed information concerning how to distinguish between the APLv and NPM 1+ AMLs with a dominant immature myeloid (blastic) component (b NPM1+ AML) by FCM is scarce (Ferrari et al, 2012 ).…”