title: Evaluation of new markers for minimal residual disease monitoring in B-cell precursor acute lymphoblastic leukemia: CD73 and CD86 are the most relevant new markers to increase the efficacy of MRD 2016; 00B: 000-000.
abstract: Multiparametric flow cytometry (MFC) is a popular technique for minimal residual disease (MRD) analysis. However, its applicability is still limited to 90% of B-cell precursor acute lymphoblastic leukemia (BCPALL) due to two major issues, i.e. a proportion of cases do not express adequate leukemia associated immunophenotype (LAIPs) with currently used markers and drug-induced antigen modulation. Hence, the incorporation of additional reliable markers is required for the further improvement of MFC-based MRD evaluation. We studied the utility of new markers in improvising MFC-based MRD detection in BCPALL.
  
  
  
  Expression-patterns of six new markers, i.e. CD24, CD44, CD72, CD73, CD86, and CD200 were studied in leukemic-blasts from ninety childhood BCPALL patients and in hematogones from 20 uninvolved staging bone marrow (BM) and ten postinduction non-BCPALL BM samples using eight-color MFC. The utility of these new markers in the day 35 postinduction MRD evaluation was determined.
  
  
  
  Frequencies of LAIPs of CD73, CD86, CD72, CD44, CD200, and CD24 in diagnostic samples were 76.7, 56.7, 55.6, 50, 28.9, and 20%, respectively. Differential expression of all new markers was highly significant (P < 0.01) between early (CD10+ CD19+ CD34+) hematogones, late (CD10+ CD19+ CD34-) hematogones and BCPALL blasts except between early hematogones and BCPALL blasts for CD200 (P = 0.1). In MRD-positive samples, CD73 showed the maximum (83%) frequency of LAIP and CD86 showed the highest (100%) stability of aberrant expression. Inclusion of CD73 and CD86 increased the applicability of MFC-MRD assay to 98.9% MRD samples.
  
  
  
  CD73 and CD86 are the most relevant markers to incorporate in the routine MRD evaluation of BCPALL. © 2016 International Clinical Cytometry Society.
authors.affiliation: Hematopathology Laboratory, Tata Memorial Center, Mumbai, Room 727, Hematopathology Laboratory, Annexe Building, 7th Floor, Tata Memorial Hospital, Parel, 400012, Mumbai, India.
authors.forename: Prashant R
authors.initials: PR
authors.lastname: Tembhare
authors.affiliation: Hematopathology Laboratory, Tata Memorial Center, Mumbai, Room 727, Hematopathology Laboratory, Annexe Building, 7th Floor, Tata Memorial Hospital, Parel, 400012, Mumbai, India.
authors.forename: Sitaram
authors.initials: S
authors.lastname: Ghogale
authors.affiliation: Hematopathology Laboratory, Tata Memorial Center, Mumbai, Room 727, Hematopathology Laboratory, Annexe Building, 7th Floor, Tata Memorial Hospital, Parel, 400012, Mumbai, India.
authors.forename: Nisha
authors.initials: N
authors.lastname: Ghatwai
authors.affiliation: Hematopathology Laboratory, Tata Memorial Center, Mumbai, Room 727, Hematopathology Laboratory, Annexe Building, 7th Floor, Tata Memorial Hospital, Parel, 400012, Mumbai, India.
authors.forename: Yajamanam
authors.initials: Y
authors.lastname: Badrinath
authors.affiliation: Hematopathology Laboratory, Tata Memorial Center, Mumbai, Room 727, Hematopathology Laboratory, Annexe Building, 7th Floor, Tata Memorial Hospital, Parel, 400012, Mumbai, India.
authors.forename: Nikesh
authors.initials: N
authors.lastname: Kunder
authors.affiliation: Hematopathology Laboratory, Tata Memorial Center, Mumbai, Room 727, Hematopathology Laboratory, Annexe Building, 7th Floor, Tata Memorial Hospital, Parel, 400012, Mumbai, India.
authors.forename: Nikhil V
authors.initials: NV
authors.lastname: Patkar
authors.affiliation: Hematopathology Laboratory, Tata Memorial Center, Mumbai, Room 727, Hematopathology Laboratory, Annexe Building, 7th Floor, Tata Memorial Hospital, Parel, 400012, Mumbai, India.
authors.forename: Asma R
authors.initials: AR
authors.lastname: Bibi
authors.affiliation: Hematopathology Laboratory, Tata Memorial Center, Mumbai, Room 727, Hematopathology Laboratory, Annexe Building, 7th Floor, Tata Memorial Hospital, Parel, 400012, Mumbai, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Chatterjee
authors.affiliation: Department of Pediatric Oncology, Tata Memorial Center, Main Building, Ground floor, Tata Memorial Hospital, Parel, 400012, Mumbai, India.
authors.forename: Brijesh
authors.initials: B
authors.lastname: Arora
authors.affiliation: Department of Pediatric Oncology, Tata Memorial Center, Main Building, Ground floor, Tata Memorial Hospital, Parel, 400012, Mumbai, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Narula
authors.affiliation: Department of Pediatric Oncology, Tata Memorial Center, Main Building, Ground floor, Tata Memorial Hospital, Parel, 400012, Mumbai, India.
authors.forename: Shripad
authors.initials: S
authors.lastname: Banawali
authors.affiliation: Hematopathology Laboratory, Tata Memorial Center, Mumbai, Room 727, Hematopathology Laboratory, Annexe Building, 7th Floor, Tata Memorial Hospital, Parel, 400012, Mumbai, India.
authors.forename: Nilesh
authors.initials: N
authors.lastname: Deshpande
authors.affiliation: Department of Cancer Cytogenetics, Tata Memorial Center, Mumbaim, Room 726, Annexe Building, 7th Floor, Tata Memorial Hospital, Parel, 400012, Mumbai, India.
authors.forename: Prathibha
authors.initials: P
authors.lastname: Amare
authors.affiliation: Hematopathology Laboratory, Tata Memorial Center, Mumbai, Room 727, Hematopathology Laboratory, Annexe Building, 7th Floor, Tata Memorial Hospital, Parel, 400012, Mumbai, India.
authors.forename: Sumeet
authors.initials: S
authors.lastname: Gujral
authors.affiliation: Hematopathology Laboratory, Tata Memorial Center, Mumbai, Room 727, Hematopathology Laboratory, Annexe Building, 7th Floor, Tata Memorial Hospital, Parel, 400012, Mumbai, India.
authors.forename: Papagudi G
authors.initials: PG
authors.lastname: Subramanian
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual / Q000378:metabolism*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*; D055815:Young Adult
chemical_list: D051940:B7-2 Antigen; D014408:Biomarkers, Tumor; C497964:CD86 protein, human; D058851:GPI-Linked Proteins; D015720:5'-Nucleotidase; C548241:NT5E protein, human
keywords: BCPALL; CD73; CD86; MRD; flow cytometry