Impact of FLT3 Receptor (CD135) Detection by Flow Cytometry on Clinical Outcome of Adult Acute Myeloid Leukemia Patients

• Published in: Clinical lymphoma, myeloma and leukemia myeloma and leukemia, 2018-08, Vol.18 (8), p.541-547
• Main Authors: Kandeel, Eman Z., El Sayed, Ghada, Elsharkawy, Nahla, Eldin, Dalia Negm, Nassar, Hanan R., Ibrahiem, Dalia, Amin, Randa, Hanafi, Marwa, Khalil, Mohamed, Kamel, Azza
• Format: Article
• Language: English
• Subjects: AML; CD135; Flow cytometery; FLT3 receptor; FLT3-ITD
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/j.clml.2018.05.014

In a large study focusing on the impact of CD135 on clincal presentation and its relation to other prognostic parameters, we addressed whether CD135 could be predictor of FMS-like tyrosine kinase 3 (FLT3) mutation. We found an association between CD135 expression and persistence of positive minimal residual disease postinduction status. CD135 is a crucial indicator of unfavorable outcome that influences complete remission status, disease-free survival, and overall survival in adult Egyptian acute myeloid leukeia patients. The significance of FMS-like tyrosine kinase 3 (FLT3)-ITD mutation in acute myeloid leukemia (AML) prognosis has been well established. The aims of this study were to investigate the prognostic impact of the FLT3 protein (CD135) expression and its association with FLT3-ITD mutation, and to identify its role in minimal residual disease. CD135 was measured by flow cytometry on leukemic blasts of 257 adults with de novo AML. High expression of CD135 ≥ 20% was correlated with clinical, laboratory, and other prognostic factors that influenced treatment outcome. FLT3-ITD mutation was tested by PCR. The frequency of CD135 expression was 138 (53.7%) of 257. FLT3-ITD was detected in (21.4%). Positive CD135 expression was associated with high total leukocyte count (P = .006), platelet count (P = .003), monocytic leukemia (P < .001), and CD34 (P = .008) and CD117 (P = .006) expression. CD135 expression ≥ 25% was a predictor of FLT3-ITD mutation (P = .03). CD135 overexpression was a negative predictor of complete remission and of postinduction minimal residual disease at days 14 and 28 (P < .001). CD135 had an adverse impact on overall and disease-free survival (68.5% vs. 15%, P = .002). Multivariate analysis indicated CD135 was the sole independent prognostic factor for overall survival (hazard ratio = 2.49; 95% confidence interval, 1.855-3.345; P < .001). CD135 is emerging as a prognostic factor, a new marker for minimal residual disease, and a potential novel therapeutic target of AML.