ABSTRACT
This study aimed to address the prognostic relevance of CD34+/CD38-/TIM3+ leukemic stem cell (LSC) frequency in patients with acute myeloid leukemia (AML) and its impact on patient outcome. We analyzed the expression of LSC markers (CD34+/CD38-/TIM3+) using flow cytometry in bone marrow samples of 53 AML cases before and after induction chemotherapy. The LSC frequency at diagnosis was significantly higher compared with that postinduction (P < .001). Patients were categorized into high LSC expressers (≥ median) and low expressers (< median). Patients with AML with high number of LSCs at diagnosis had significantly lower induction of remission response (P = .0104), shorter disease-free survival, and shorter overall survival (P < .001 for both) compared with those with lower LSC count. Cox regression analysis revealed that LSC frequency at diagnosis is an independent prognostic factor in AML. Assessment of LSCs (CD34+/CD38-/TIM3+) at diagnosis is recommended for refining of AML risk stratification.
Subject(s)
ADP-ribosyl Cyclase 1/metabolism , Antigens, CD34/metabolism , Hepatitis A Virus Cellular Receptor 2/metabolism , Leukemia, Myeloid, Acute/pathology , Membrane Glycoproteins/metabolism , Neoplastic Stem Cells/pathology , Adult , Biomarkers, Tumor/metabolism , Female , Flow Cytometry , Humans , Immunophenotyping , Induction Chemotherapy , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Neoplastic Stem Cells/metabolism , Prognosis , Remission Induction , Survival AnalysisABSTRACT
The role of cortactin in T-cell acute lymphoblastic leukemia (T-ALL) tissue infiltration has been previously reported. However, its impact on patients' responsiveness to therapy and patient's outcome was not previously addressed. This study was conducted on 60 T-ALL pediatric patients at diagnosis and 10 nonleukemic controls. Cortactin and HS1 expressions were identified by real-time polymerase chain reaction. Cortactin and HS1 expression were significantly higher in T-All patients as compared with controls as well as postinduction levels (P≤0.001 for both). The high cortactin expression was significantly associated with high peripheral white cell counts (P≤0.001), blood blast cells (P≤0.001) and central nervous system (CNS) infiltration (P≤0.001), and early precursor T-ALL subtype (P≤0.001) as compared with the remaining groups. The induction of remission response was significantly higher in T-ALL patients with lower cortactin expression levels as compared with T-ALL patients with higher one (P≤0.001). The high cortactin and HS1 expressions were significantly predictors of CNS infiltrations (hazard ratios [HR]: 1.051, confidence interval [CI]: 1.02-1.13, P=0.04 and HR: 1.87, CI: 1.23-2.091, P=0.002, respectively) and bone marrow relapse (HR: 1.43, CI: 1.18-1.92, P=0.004 and HR: 1.07, CI: 1.01-1.24, P=0.002, respectively). Furthermore, high cortactin expression levels were associated with shorter B-ALL patients' overall survival as compared with those with lower cortactin levels (P=0.002). In conclusion, high expression of cortactin and/or HS1 at diagnosis is a bad prognostic marker of T-ALL patients' outcome. Moreover, cortactin and/or HS1 expression could be used as a biomarker for refining risk stratification of T-ALL.
