ABSTRACT
Acute myeloid leukemia (AML) accounts for approximately 20% of all pediatric acute leukemias. The outcome of AML is still unsatisfactory. CD123 and CD200 were demonstrated to play important roles in hematological malignancies. The aim of this study was to investigate the impact of CD200 and CD123 overexpression and the influence of both proteins on the clinical presentation and disease outcome. Bone marrow (BM) samples from 89 pediatric AML patients were obtained at presentation and after therapy. Cells from the bulk population and from the leukemia stem cell (LSC) compartment were examined by multi parametric flow cytometry. In the bulk population, CD200 was positive in 64/89 (71.9) samples, CD123 was positive in 62/89 (69.7%) samples, and dual CD200 and CD123 positivity was observed in 54/89 (60.7%) samples. CD200/CD123 expressions were observed in LSCs in 64/60 samples respectively (71.9%/67.4%), and co-expressed in 51 samples (57.3%). CD200 was overexpressed in secondary AML (p < 0.05). A multivariate analysis revealed that minimal residual disease (MRD) and lymphadenopathy were associated with CD200 overexpression. Moreover, lymphadenopathy, low platelet count, and MRD were independently associated with CD123 expression. The co-expression of CD200 and CD123 demonstrated a statistically significant relationship with unfavorable cytogenetic karyotypes and high total leucocyte count (TLC). The expression of CD200 and CD123 alone and together had an adverse impact on complete remission (CR), MRD positivity, and overall survival (OS). Cases with MRD on day 28 after induction displayed stable expression patterns of CD200 and CD123. CD200 and CD123 both had a negative influence on clinical presentation and treatment outcome, which remarkably worsened when both were concomitantly overexpressed. CD200 and CD123 can therefore be used as markers of MRD in AML and may also serve as therapeutic targets.
Subject(s)
Antigens, CD/metabolism , Biomarkers/metabolism , Interleukin-3 Receptor alpha Subunit/metabolism , Leukemia, Myeloid, Acute/pathology , Neoplastic Stem Cells/pathology , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Leukemia, Myeloid, Acute/metabolism , Male , Neoplastic Stem Cells/metabolism , Prognosis , Survival RateABSTRACT
We have investigated the frequency and the effect of KIT mutations on the outcome of patients with CBF-AML. 69 patients (34 pediatrics and 35 adults) with CBF-AML were enrolled in the study. The frequency of KIT mutations was higher in adults compared to pediatrics (22.9% and 14.7%, pâ¯=â¯0.38) respectively. Leukocytosisâ¯≥â¯20â¯×â¯109 /L was significantly associated with pediatrics compared to adults. t(8;21)(q22;22) was significantly associated with thrombocytopenia in adults. We conclude that no significant difference is found between KIT mutated and unmutated CBF-AML in adults and pediatrics. Children with CBF-AML present with leukocytosis. t(8;21) is associated with thrombocytopenia.
ABSTRACT
BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSION: CD135 is emerging as a prognostic factor, a new marker for minimal residual disease, and a potential novel therapeutic target of AML.
