PB1702 EXPRESSION OF ANGIOTENSIN‐CONVERTING ENZYME IN PATIENTS WITH ACUTE LEUKEMIAS

Abstract

Background:Blast cells are characterized by aberrant expression normal markers of early hematopoietic progenitor cells (HPC). Angiotensin‐converting enzyme (ACE/CD143), a key regulator of renin‐angiotensin system, was shown to be expressed in blood‐forming tissues of the human embryo and primitive human HPC. Recent studies indicated that CD143 is over‐expressed in leukemic myeloid blast cells.Aims:To evaluate the surface expression of CD143 in blast cells in patients with newly diagnosed acute leukemia (AL).Methods:The expression of CD143 was estimated in patients with newly diagnosed untreated acute leukemia, using eight‐color flow cytometry. The blast gate was defined on the basis of CD45dim expression and side‐scatter characteristics. Anti‐CD143 monoclonal antibody (clone BB9, BD) conjugated with phycoerythrin was used for analysis of CD143 expression. The percentage of positive cells (PPC) and the mean fluorescence intensity (MFI) was applied to describe expression. The expression of CD143 was devided into three groups according range of PPC ≤1%, 1 – 20 %, and ≥20 %.Results:A total of untreated 68 patients with newly diagnosed acute leukemia were included in the study group. They were diagnosed with non‐promyelocytic acute myeloid leukemia (non‐APL AML) – 35 (51.5 %), of them 3 (8.5 %) patients were related to favorable genetic group, 9 (25.7 %) – intermediate, 23 (65.8 %) – adverse; promyelocytic leukemia (APL) – 10 (14.7 %); B acute lymphoblastic leukemia/lymphoma (B‐ALL) – 13 (19.1 %), including 2 patients with Ph‐positive B‐ALL; T acute lymphoblastic leukemia/lymphoma (T‐ALL) – 10 (14.7 %), including 2 cases of early T‐precursor ALL (ETP). Median age of patients was 35.5 years, 29 male, 39 female.In total group with CD143 expression with PPC≥20% was observed in 7% (5/68) of all cases AL. CD143 expression in non‐APL AML with a range of PPC 1 – 20 % was detected in 12/35 cases (34.2 %), PPC ≥20 % was observed in 2/35 cases with complex karyotype (5.7 %). In group with APL 2/10 (20 %) patients had 1 – 20%, and 2/10 (20 %) patients had >20 %. Among T‐ALL only 1/10 (10 %) had a CD143 expression. ACE expression in B‐ALL was absent (defined as ≤1 %). Median MFI of ACE expression was higher in patients with APL – 477 (range 159 – 4796) than in non‐APL AML ‐ 175 (range 43 – 3253). CD143 expression with PPC≥1% was significantly higher in patients with AML (non‐APL AML and APL), than in ALL (B‐ and T‐ALL), 40 % (18/45) vs. 4.3 % (1/23) (p = 0.0016).Summary/Conclusion:Thus, CD143 expression with PPC≥20% was observed only in 7% (5/68) of all cases AL, 2 was observed in AML with PML‐RARA, 2 ‐ AML with complex karyotype and 1 in ETP‐ALL. No expression of CD143 was detected in B‐ALL. CD143 expression was significantly higher in myeloid blast cells than lymphoid. No correlation was found between the expression of ACE and age, sex, neuroleukemia, leucocytes count, bone marrow blasts, lactic acid dehydrogenase activity and cytogenetic abnormalities in different subgroups. The significance of CD143 expression in AL is not completely clear and has to be studied.