title: Immunophenotypic Modulation of the Blast Cells in Childhood Acute Lymphoblastic Leukemia Minimal Residual Disease Detection.
abstract: Early clearance of leukemic cells during induction therapy of childhood acute lymphoblastic leukemia (ALL) is a basis for treatment optimization. Currently, the most widely used methods for the detection of minute residual malignant cells in the bone marrow and/or peripheral blood, minimal residual disease (MRD), are PCR and flow cytometry (FCM). Immunophenotypic modulation (IM) is a well known factor that can hamper the accurate FCM analysis.
  
  
  
  To report the IM detected by 8-color FCM during the BFM-type remission induction in 24 consecutive MRD-positive samples of children with B-cell precursor ALL and the possible implications for MRD detection.
  
  
  
  Between 2010 and 2012 we prospectively followed up the MRD on days 15 and 33 of induction treatment in bone marrow (BM) samples and on day 8 in peripheral blood (PB). The IM was assessed by comparative analyses of the changes in the mean fluorescence intensity of 7 highly relevant antigens expressed by the leukemic cells and normal B-lymphocytes.
  
  
  
  IM occurred, to different extents, in all analyzed day 15 BM and in most day 33 BM samples. Statistically significant changes in the MFI-levels of four CDs expressed by the leukemic blasts were observed: downmodulation of CD10, CD19 and CD34 and upmodulation of CD20. No changes in the expression of CD38, CD58 and CD45 were noticed.
  
  
  
  Measuring the MRD by standardized 8-color flow cytometry helps improve the monitoring of the disease, leading to better therapeutic results. However, the IM of the different antigens expressed by the leukemic blasts should be taken into consideration and cautiously analyzed.
authors.affiliation: Department of Pediatrics and Medical Genetics, Medical University of Plovdiv, Plovdiv, Bulgaria
authors.forename: Hasan A
authors.initials: HA
authors.lastname: Burnusuzov
authors.affiliation: Department of Pediatrics and Medical Genetics, Medical University of Plovdiv, Plovdiv, Bulgaria
authors.forename: Mariya I
authors.initials: MI
authors.lastname: Spasova
authors.affiliation: Department of Microbiology and Immunology, Medical University of Plovdiv, Plovdiv, Bulgaria
authors.forename: Mariana A
authors.initials: MA
authors.lastname: Murdjeva
authors.affiliation: Department of Pediatrics and Medical Genetics, Medical University of Plovdiv, Plovdiv, Bulgaria
authors.forename: Angelina A
authors.initials: AA
authors.lastname: Stoyanova
authors.affiliation: Department of Pediatrics and Medical Genetics, Medical University of Plovdiv, Plovdiv, Bulgaria
authors.forename: Ivan N
authors.initials: IN
authors.lastname: Mumdziev
authors.affiliation: Department of Pediatrics and Medical Genetics, Medical University of Varna, Varna, Bulgaria
authors.forename: Valeriya I
authors.initials: VI
authors.lastname: Kaleva
authors.affiliation: Department of Pediatrics and Medical Genetics, Medical University of Varna, Varna, Bulgaria
authors.forename: Milena I
authors.initials: MI
authors.lastname: Belcheva
authors.affiliation: Department of Pediatrics and Medical Genetics, Medical University of Plovdiv, Plovdiv, Bulgaria
authors.forename: Miroslava N
authors.initials: MN
authors.lastname: Bosheva
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D000293:Adolescent; D018941:Antigens, CD19 / Q000276:immunology; D018951:Antigens, CD20 / Q000276:immunology; D018952:Antigens, CD34 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow; D001854:Bone Marrow Cells / Q000276:immunology*; D018968:CD58 Antigens / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D060828:Induction Chemotherapy; D007223:Infant; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D015260:Neprilysin / Q000276:immunology; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D011446:Prospective Studies
chemical_list: D018941:Antigens, CD19; D018951:Antigens, CD20; D018952:Antigens, CD34; C000604811:CD19 molecule, human; D018968:CD58 Antigens; D008562:Membrane Glycoproteins; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D015260:Neprilysin