CD123 expression levels in 846 acute leukemia patients based on standardized immunophenotyping

Abstract

Background While it is known that CD123 is normally strongly expressed on plasmacytoid dendritic cells and completely absent on nucleated red blood cells, detailed information regarding CD123 expression in acute leukemia is scarce and, if available, hard to compare due to different methodologies. Methods CD123 expression was evaluated using standardized EuroFlow immunophenotyping in 139 pediatric AML, 316 adult AML, 193 pediatric BCP‐ALL, 69 adult BCP‐ALL, 101 pediatric T‐ALL, and 28 adult T‐ALL patients. Paired diagnosis‐relapse samples were available for 57 AML and 19 BCP‐ALL patients. Leukemic stem cell (LSC) data was available for 32 pediatric AML patients. CD123 expression was evaluated based on mean fluorescence intensity, median fluorescence intensity, and percentage CD123 positive cells. Results EuroFlow panels were stable over time and between laboratories. CD123 was expressed in the majority of AML and BCP‐ALL patients, but absent in most T‐ALL patients. Within AML, CD123 expression was lower in erythroid/megakaryocytic leukemia, higher in NPM1 mutated and FLT3‐ITD mutated leukemia, and comparable between LSC and leukemic blasts. Within BCP‐ALL, CD123 expression was higher in patients with (high) hyperdiploid karyotypes and the BCR‐ABL fusion gene. Interestingly, CD123 expression was increased in BCP‐ALL relapses while highly variable in AML relapses (compared to CD123 expression at diagnosis). Conclusions Authors evaluated CD123 expression in a large cohort of acute leukemia patients, based on standardized and reproducible methodology. Our results may facilitate stratification of patients most likely to respond to CD123 targeted therapies and serve as reference for CD123 expression (in health and disease). © 2018 The Authors. Cytometry Part B: Clinical Cytometry published by Wiley Periodicals, Inc. on behalf of International Clinical Cytometry Society.

Issue Highlights – March 2019

“…Immunophenotyping was performed using standardized procedures as developed by the EuroFlow collaborative project . Whilst published information on this topic was relatively scarce and difficult to compare due to different methodologies, Bras and colleagues confirmed most observations as they extensively document in this report . Importantly, they observed that in paired B‐cell precursor ALL, CD123 expression was considerably higher at relapse than at initial diagnosis, whilst in AML, the leukemic stem cells (CD34 pos , CD38 neg fraction of tumor cells) expressed similar CD123 levels as the remainder of AML blasts.…”

Applications of Flow Cytometric Immunophenotyping in the Diagnosis and Posttreatment Monitoring of B and T Lymphoblastic Leukemia/Lymphoma

“…With the improvements in induction therapy for pediatric B lymphoblastic leukemia, attention is gradually shifting to later time points from therapy, End of Consolidation in particular, in order to identify patients who have had inadequate response to initial therapy and who might benefit from one of multiple novel treatments now available, for example, anti-CD19 or anti-CD22 therapy. To this end, new reagents have been identified that may allow improved discrimination of hematogones from residual leukemia (17), a few of which have been demonstrated to be of potential value in defined reagent combinations tested on patient cohorts (18)(19)(20), these include CD49f (21), CD81 (22), CD123 (23), CD73 (20,24) (see Fig. 9), CD86 (20,24), and CD304 (24).…”

“…The same excellent outcome for MRD negative patients is not seen in the high-risk population, emphasizing the importance of the underlying biology in interpreting the significance of MRD. In parallel, a higher sensitivity flow cytometric assay has been developed that involves the collection of larger numbers of total events with an expanded antibody panel (18,19). This assay requires more involved specimen processing and longer acquisition times with the potential for the observation of new artifacts.…”

The role of interleukin-3 and its receptor in acute leukemia pathogenesis

“…По мере дифференцировки клетки-предшественницы экспрессия α-цепи рецептора к ИЛ-3 увеличивается на клетках миелоидного ростка и сохраняется до поздних стадий созревания [30]. Низкая экспрессия сохраняется на гранулоцитах, несколько выше она бывает на эозинофилах и моноцитах [30]. Базофилы и плазмоцитоидные дендритные клетки (ПДК) характеризуются наиболее высокой экспрессией CD123.…”

“…Базофилы и плазмоцитоидные дендритные клетки (ПДК) характеризуются наиболее высокой экспрессией CD123. Мембранная экспрессия рецептора на ПДК отличается самыми высокими значениями интенсивности флюоресценции, отражающей плотность экспрессии рецептора при иммунофенотипическом исследовании [30].…”